challenges of covid - academie-medecine.fr · @acadmed Académie nationale de médecine. Created...

Tuesday, June 16, 20209:30am to 5:30pm

the challenges of covid-19The french Academy of Medicinebrings together its partners worldwide

Under the High Patronage ofMr Emmnanuel MACRON

President of the French Republic

Sous le Haut Patronage deMonsieur Emmnanuel MACRON

Président de la République

INTERNATIONAL WEBINARAs part of the Bicentenary

FranceBrazil ChinaCanada

United States of America

ItaliaIsrael

Gabon

Sweden

Cameroon Germany

United KingdomMorocco

1820 - 20202

Editorial of the Chair of the international relationship Committee of French Academy of Medicine, Pr. Patrice DEBRÉ

Speech of the President of the French Academy of Medicine, Pr. Jean-François MATTEI

Program

List of speakers

Speakers presentations

Creation of the french academy of medicine and the chalenge of epidemics in history, Pr. Patrice DEBRÉ

Public policies and strategies against SARS-CoV-2FRANCE The forgotten preparedness strategy, Pr. Didier HOUSSIN

MOROCCO Response Strategy and Epidemiological Situation in Morocco, Pr. Moulay Hicham AFIF

UNITED KINGDOM Dr. Brian MC CLOSKEY Presentation

GERMANY Lessons Learned from COVID-19 : Results and Development of Global Health in Germany, Pr. Detlev GANTEN

SWEDEN Pr. Johan GIESECKE Presentation

Pathophysiology of COVID-19GABON From coronaviruses to SARS-CoV-2, Dr Avelin AGHOKENG

ITALY Child presentations and Kawasaki-like syndrome, Pr. Angelo RAVELLI

ISRAEL Characterizations of the cytokine storm in patients with COVID-19, at Hadassah-Hebrew University Medical Center, Pr. Dror MEVORACH

COVID-19 and therapeutic trialsFRANCE The French strategy, Pr. Yazdan YAZDANPANAH

QUEBEC COVID-19 & clinical trial - Quebec’s key features, Dr. Carole JABET

USA COVID-19 and Therapeutic Trials, Pr. Carlos DEL RIO

COVID-19 and vaccine trialsUSA Vaccine candidates against SARS-CoV-2, Pr. Stanley PLOTKIN

UNITED KINGDOM A Chimpanzee Adenoviral Vectored Vaccine against COVID-19, Pr, Adrian HILL

GERMANY MVA-SARS-2-S DZIF COVID-19 vaccine candidate for risk groups, Pr. Gerd SUTTER

FRANCE How to accelerate vaccine development by protecting volunteers and future vaccines, Dr Marco CAVALERI

French scientific council COVID-19FRANCE Expertise and decision support in health crisis, Pr. Jean-François DELFRAISSY

Conclusion of the Perpetual Secretary of the French Academy of medeicine, Pr. Jean François ALLILAIRE

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SUMMARY

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Editorial du Président du Comité des affaires internationales de l’Académie nationale de médecine, Pr. Patrice DEBRÉ

Discours du Président de l’Académie nationale de médecine, Pr. Jean-François MATTEI

Programme

Liste des orateurs

Présentations des orateurs

Création de l’Académie de médecine de France et défi des épidémies, Pr. Patrice DEBRÉ

Politiques publiques et stratégies contre le SARS-CoV-2FRANCE La stratégie de préparation oubliée, Pr. Didier HOUSSIN

MAROC Stratégie de réponse et situation épidémiologique au Maroc, PR. Moulay Hicham AFIF

ROYAUME-UNI Présentation du Dr. Brian MC CLOSKEY

ALLEMAGNE Leçons tirées du COVID-19 : résultats et développement de la santé mondiale en Allemagne, Pr. Detlev GANTEN

SUÈDE Présentation du Pr. Johan GIESECKE

Pathophysiologie de la COVID-19GABON Des coronavirus au SARS-CoV-2, Dr Avelin AGHOKENG

ITALIE Présentations d’enfants et syndrome de type Kawasaki, Pr. Angelo RAVELLI

ISRAËL Caractérisations de la tempête de cytokines chez les patients atteints de la COVID-19, au Centre médical universitaire Hadassah-Hebrew, Pr. Dror MEVORACH

COVID-19 et essais thérapeutiquesFRANCE La stratégie française, Pr. Yazdan YAZDANPANAH

QUÉBEC COVID-19 et essai clinique - Les principales caractéristiques du Québec, Dr. Carole JABET

ETATS-UNIS COVID-19 et essais thérapeutiques, Pr. Carlos DEL RIO

COVID-19 et essais vaccinauxETATS-UNIS Les vaccins candidats contre le SARS-CoV-2, Pr. Stanley PLOTKIN

ROYAUME-UNI Un vaccin à vecteur adénoviral de chimpanzé contre la COVID-19, Pr, Adrian HILL

ALLEMAGNE Le vaccin candidat MVA-SARS-2-S DZIF COVID-19 pour les groupes à risque, Pr. Gerd SUTTER

FRANCE Comment accélérer le développement de vaccins en protégeant les volontaires et futurs vaccins ? Dr Marco CAVALERI

Expérience du conseil scientifique français COVID-19FRANCE Expertise et aide à la décision en crise sanitaire, Pr. Jean-François DELFRAISSY

Conclusion du Secrétaire perpétuel de l’Académie nationale de médecine, Pr. Jean François ALLILAIRE

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SOMMAIRE

1820 - 20204

Quand l’Académie nationale de médecine rencontre ses partenaires du Monde autour des problématiques de la pandémie Covid-19 à l’occasion de deux cents ans de lutte contre les épizooties

Le webinaire international sur la Covid-19 s’inscrit comme l’une des principales manifestations du bicentenaire de notre Académie, mais aussi comme une de nos initiatives et ambitions dédiées à l’international.

L’Académie de médecine, créé le 20 décembre 1820 pour conseiller le gouvernement et la Royauté sur les politiques publiques en santé, s’affirma d’emblée comme une instance couvrant les différents aspects de la médecine grâce à la diversité des spécialités médicales, chirurgicales et pharmaceutiques de ses membres provenant de champs scientifiques divers. La présence de ses membres étrangers marque de manière incontestable le caractère international de la Santé.

L’année 2020, qui célèbre, 200 ans plus tard cette création, est l’occasion de rappeler que les relations internationales sont une de nos principales priorités au profit de la santé pour tous.

L’Académie de médecine s’enorgueillit aujourd’hui de 180 membres étrangers ainsi que de nombreux partenariats avec des académies étrangères avec lesquelles elle souhaite renouveler ses liens tant avec ses membres correspondants qu’associés présents et futurs de notre institution.

Les diverses collaborations qui en découlent répondent aux initiatives pour renforcer les interactions internationales et le partage d’expériences. Les priorités stratégiques de notre politique sont ainsi de favoriser les activités internationales en multipliant les rencontres présentielles et en distancielles autour de sujets d’intérêt choisis en commun. Celles-ci se tournent vers des partenariats historiques et des rencontres vers nos amis de la francophonie, mais plus largement s’ouvrent aux multiples problèmes de la mondialisation.

Le comité des Affaires internationales favorise également une politique de rencontres avec les Alumni pour permettre une plus grande transmission d’information sur les opportunités françaises en matière de soins, de recherche et formation. L’ANM s’inscrit également dans l’expertise souhaitée par les actions interacadémiques ainsi celles de l’Interacademy partnership (IAP) et de la Fedération of European Academies of Medicine (FEAM). La Covid-19, sujet majeur d’inquiétude, pour le monde entier, nous donne aujourd’hui l’occasion de ce webinaire permettant de montrer les multiples aspects des conduites et confrontation des politiques publiques et d’aborder les différentes recherches en physiopathologie, thérapeutique et vaccins. Nous avons souhaité cette expertise croisée des différents pays pour le meilleur partage de l’actualité liée à cette maladie.Cette journée est ainsi un lieu de rencontre qui, bien que virtuel, est destiné à partager l’état de l’art et la science.

Tout en s’inscrivant dans une démarche historique elle représente le renouveau et le développement de partenariats dans la lutte contre les épidémies et plus largement pour la Santé du Monde où l’Académie nationale de médecine de France souhaite prendre toute sa place.

ÉDITOProfessor Patrice DEBRÉ Chair of the international relationship Committee of the French Academy of MedicinePrésident du Comité des affaires internationales de l’Académie nationale de médecine

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When the French National Academy of Medicine (ANM) meets its partners around the world about Covid-19 on the occasion of two hundred years of fighting against epizootics

The Covid-19 webinar is one of the main bicentennial events of our National Academy of Medicine, but also one of our initiatives and ambitions dedicated to the international.

The French National Academy of Medicine was created on December 20, 1820, to advise government and royalty on public health policy. With its members belonging to various medical, surgical and pharmaceutical specialties, but also its associate members from various scientific fields, the ANM immediately asserted itself as a body covering the different aspects of medicine. Already, in a notable way, it welcomed the presence of international members, indicating that health has no borders and is nourished by its foreign partnerships. The year 2020, which celebrates 200 years later this creation, is the opportunity to recall this initiative, and better still to make International Relationships one of our main lines of conduct and strategy.

Today, the Academy of Medicine hosts 180 foreign members as well as numerous partnerships with foreign academies. The various collaborations that result respond to different initiatives but are better dedicated to strengthening international interactions and sharing of experience. The strategic priorities of our policy are thus to promote regional loco activities by supporting face-to-face meetings and Visioconferences around subjects of interest chosen in common. These look to historical partnerships and the meeting of those of the Francophonie, but more broadly are open to the many problems of globalization. ANM strategy also seeks to promote a policy of meeting with Alumni and to allow a transfer of information concerning French opportunities in terms of care, research, and training. The ANM is also part of the expertise desired by interacademic activities, as those of the interacademy partnership (IAP) and Federation of European Academies of Medicine (FEAM). Last but not least the ANM wishes to renew its links with the present and future foreign associates and correspondents who are members of our institution.

In continuation of the fight against epidemics, one of the first mission entrusted to the Academy since its creation, The Covid which is a major subject of concern for the whole world gives us today the opportunity of this webinar. We wanted it to be able to show the multiple aspects of the conduct and confrontation of public policies, discussing actualities concerning research in physiopathology, therapy and vaccines. We also wanted to cross the expertise of different countries for the best sharing of news related to this disease.This day was thus a scientific meeting which, although virtual, was intended to share the state of the art and science about Covid-19. In the continuation of a historic approach, it represents the renewal and development of a partnership for the fight against epidemics, and, more broadly, for global health, where ANM wishes to fully act.

1820 - 20206

« C’est pour notre compagnie, un très grand honneur, mais aussi un grand plaisir de vous accueillir aujourd’hui à l’occasion de la première cérémonie du bicentenaire de notre Académie. Il y 200 ans en effet qu’était créé notre établissement, à l’ombre déjà d’autres épidémies, typhus, choléra, fièvre jaune, mais aussi de débats qu’alimentaient la compréhension sur le rôle des microbes et leur lutte. Ce programme consacré à la pandémie de Covid-19 rapproche ainsi les deux actualités, celle d’aujourd’hui et du siècle

de l’hygiène et des premières découvertes sur les maladies infectieuses. Il était également naturel que l’événement soit dédié à l’international, car plus que jamais l’infection par le Coronavirus qui a terrassé le monde, montre que la santé est un bien public mondial.

Certes, sans revenir à l’histoire, nombre d’éléments rappellent les initiatives de notre pays en faveur d’une Santé mondiale et le soutien de notre Académie à celle-ci.

Permettez-moi d’en rappeler quelques-uns, notamment dans le cadre de la lutte contre les grandes pandémies. Outre l’expertise mise en œuvre dans différentes activités médicales et scientifiques à travers des partenariats bilatéraux, la France a incité et participé au début des années 2000 à la création de plusieurs organisations multilatérales dédiées aux grandes pandémies telles le Fonds mondial de lutte contre le Sida, le paludisme et la tuberculose, Unitaid, ainsi que, pour la recherche, l’EDCTP. (European and development clinical trial Partnership)

La France possède un modèle de santé porteur de valeurs fortes : dont la solidarité, l’équité des services de santé, leur accès, ainsi que leurs qualités, font partie. Il en est ainsi, également, pour notre modèle de couverture d’assurance maladie, message porté au-delà des frontières.

Le rayonnement de la recherche française est reconnu depuis plusieurs siècles et a été couronné par 13 attributions de prix Nobel de physiologie et médecine.

Notre pays dispose d’un réseau international d’établissements de recherche d’excellent niveau, qui effectuent des recherches en biologie et médecine dans le cadre d’aide au développement, ce qui les met ainsi en phase avec les objectifs du millénaire. L’expertise médicale française s’inscrit également dans le jumelage d’un certain nombre d’universités et hôpitaux avec de nombreux centres hospitaliers européens et du Sud.

Pourtant tous ces efforts qui vont dans le bon sens, ont été insuffisants pour lutter contre l’émergence infectieuse d’aujourd’hui. Notre monde bouge, ses menaces, comme ses avancées en recherche et technologies. Nos systèmes de santé ont été débordés, désorganisés par le fléau. Au siècle de l’intelligence artificielle, l’épidémie a montré qu’elle se propage presque aussi vite que nos communications. Nous sommes face à de nouveaux challenges qui doivent nous faire évoluer à la vitesse des microbes. La riposte est l’affaire de tous.

Notre Académie, avec ses 295 membres nationaux et ses 180 membres étrangers apporte et apportera ses contributions à cet effort international pour la santé mondiale, notamment pour la lutte contre les pandémies et leur émergence. Nous devrons œuvrer ensemble afin de trouver les traitements et vaccins, mais ces efforts doivent aussi se laisser guider par des principes que nous défendons : « L’universalité », afin que la santé soit accessible à tous, « La solidarité » pour compenser les disparités économiques et sociales et favoriser la lutte contre la stigmatisation. La « Sécurité et protection sanitaire » pour réduire les tensions entre les pays, accroître les chances de liberté, et protéger les droits fondamentaux.

Nous avons deux cents ans d’histoire académique derrière nous, mais c’est d’avenir qu’il s’agit. Bâtissons-le ensemble dans le combat contre la Covid-19. Que cette journée, basée sur la science, soit l’occasion d’y réfléchir par des initiatives conjointes en soin, recherche et formation, en France, en Europe et à l’International. »

Seul le prononcé fait foi.

DISCOURS DU PRÉSIDENTProfessor Jean-François MATTEIPresident of the French Academy of Medicine Président de l’Académie nationale de médecine

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« It is a great honor for our company, but also a great pleasure to welcome you today on the occasion of the first bicentenary ceremony of our Academy. It has been 200 years since our establishment was created, in the shadow of other epidemics, typhus, cholera, yellow fever, etc... but also of debates that fueled understanding on the role of microbes and their fight. This program devoted to the Covid-19 pandemic thus brings together the two current events, that of today and the century of hygiene and the first discoveries on infectious diseases. It was also natural that the event should be dedicated to the international scene, because more than ever the infection by the Coronavirus which has devastated the world, shows that health is a global public good.

Certainly, without going back in history, many elements recall our country’s initiatives in favor of world health, and the support of our Academy for it.

Let me remind you of a few, particularly in the context of the fight against major pandemics. In addition to the expertise implemented in various medical and scientific activities through bilateral partnerships, France encouraged and participated in the early 2000s in the creation of several multilateral organizations dedicated to major pandemics such as the Global Fund to Fight AIDS , tuberculosis and malaria, Unitaid, as well as, for research, EDCTP, the European and development clinical trial Partnership.

France has a health model with strong values. Solidarity, equity in health services, of which their access, as well as their qualities, are part. This is also the case for our model of health insurance coverage, a message carried across borders.

The influence of French research has been recognized for several centuries and has been crowned with 13 awards of Nobel prizes in physiology and medicine.

Our country has an international network of excellent research institutions, which carry out research in biology and medicine within the framework of development aid, which thus puts them in phase with the objectives of the millennium. French medical expertise is also part of the partnership of a number of universities and hospitals with numerous European and southern hospital centers.

Yet all these efforts, which are going in the right direction, have been insufficient to fight against the infectious emergence of today. Our world is moving, its threats, as well as its advances in research and technologies. Our health systems have been overwhelmed, disorganized by the scourge. In the century of artificial intelligence, the epidemic has shown that it is spreading almost as fast as our communications. We are facing new challenges which must make us evolve at the speed of microbes. Response is everyone’s business.

Our Academy, with its 295 national members and its 180 foreign members, makes and will make its contributions to this international effort for global health, in particular for the fight against pandemics and their emergence. We will have to work together to find treatments and vaccines, but these efforts must also be guided by the principles that our Academy defends : « Universality », so that health is accessible to all, « Solidarity » to compensate for economic disparities and social issues and promote the fight against stigma. The « Health security and protection» to reduce tensions between countries, increase the chances of freedom, and protect fundamental rights

We have two hundred years of academic history behind us, but this is the future that it is all about.Let us build it together in the fight against Covid-19. May this day, based on science, be an opportunity to reflect on it through joint initiatives in care, research, and training, in France, in Europe, and at the International. »

Only the pronouncement is authentic.

1820 - 20208

9:30am OPENING

9:4010:00am

WORLD OF WELCOMEJean-François Mattei, President of the French Academy of medicine, FRANCE

CREATION OF THE FRENCH ACADEMY OF MEDICINE AND THE CHALENGE OF EPIDEMICS IN HISTORY

Patrice Debré, FRANCE

10:0012:00am

PUBLIC POLICIES AND STRATEGIES AGAINST SARS-CoV-2 Chairmen : Patrick Netter, Arnold Migus, FRANCE

Didier Houssin, FRANCE - Guang Ning, CHINA - Moulay Hicham Afif, MOROCCOBrian McCloskey, UNITED KINGDOM - Detlev Ganten, GERMANY - Johan Giesecke, SWEDEN

GENERAL DISCUSSION

Break

2:00pm

PATHOPHYSIOLOGY OF COVID-19 Chairmen : Patrice Debré, Christian Boitard, FRANCE

SRAS-CoV-2 and the human Coronavirus : Avelin Aghokeng, CAMEROON-GABONChild presentations and Kawasaki-like syndrome : Angelo Ravelli, ITALIA

Cytokinic storm : Dror Mevorach, ISRAELHost genetic factors for resistance and susceptibility to SARS-CoV-2 : Laurent Abel, FRANCE

3:004:00pm

COVID-19 AND THERAPEUTIC TRIALS Chairmen : Yves Buisson, Vincent Jarlier, FRANCE

Yazdan Yazdanpanah, FRANCE - Carole Jabet, CANADAEsper G. Kallas, BRAZIL - Carlos Del Rio, UNITED STATES OF AMERICA

4:005:00pm

COVID-19 AND VACCINE TRIALS Round table

Vaccine candidates against SRAS-CoV-2 : Stanley Plotkin, UNITED STATES OF AMERICA

Panel discussion : Marie-Paule Kieny, FRANCE

The ChAd- COVID-19 vaccine candidate : Adrian Hill, UNITED KINGDOMThe MVA-SARS-2-S vaccine candidate of the German Center for Infection Research (DZIF) :

Gerd Sutter, GERMANYHow to accelerate vaccine development by protecting volunteers and future vaccines :

Marco Cavaleri, FRANCE

5:005:30pm

THE EXPERIENCE OF THE COVID-19 FRENCH SCIENTIFIC COUNCIL : Jean-Francois Delfraissy, FRANCE

ConclusionsTHE FRENCH ACADEMY OF MEDECINE AND COVID-19: LESSONS OF THE CRISIS

Jean François Allilaire, Permanent executive officer of French Academy of medicine, FRANCE

PROGRAMAll presentations are in English

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PROGRAMME9h30 OUVERTURE

9h4010h00

MOT DE BIENVENUEJean-François Mattei, Président de l’Académie nationale de médecine, FRANCE

CRÉATION DE L’ACADÉMIE DE MÉDECINE DE FRANCE ET DÉFI DES ÉPIDÉMIES Patrice Debré, FRANCE

10h0012h00

POLITIQUES PUBLIQUES ET STRATEGIES CONTRE le SARS-CoV-2Patrick Netter, Arnold Migus, FRANCE

Didier Houssin, FRANCE - Guang Ning, CHINE - Moulay Hicham Afif, MAROCBrian McCloskey, ROYAUME-UNI - Detlev Ganten, ALLEMAGNE - Johan Giesecke, SUÈDE

DISCUSSION GENERALE

Pause

14h00

PHYSIOPATHOLOGIE de la COVID-19Patrice Debré, Christian Boitard, FRANCE

Des coronavirus au SARS-CoV-2 : Avelin Aghokeng, CAMEROUN et GABONFormes cliniques de l’enfant et syndrome de type Kawasaki : Angelo Ravelli, ITALIE

L’orage cytokinique dans la COVID-19 : Dror Mevorach, ISRAELFacteurs génétiques de l’hôte : résistance et susceptibilité au SARS-CoV-2 : Laurent Abel, FRANCE

15h0016h00

COVID-19 et ESSAIS THERAPEUTIQUESYves Buisson, Vincent Jarlier, FRANCE

Yazdan Yazdanpanah, FRANCE - Carole Jabet, CANADA Esper G. Kallas, BRESIL - Carlos Del Rio, ETATS-UNIS D’AMERIQUE

16h0017h00

COVID-19 et ESSAIS VACCINAUXTable ronde

Les vaccins candidats contre le SRAS-CoV-2 : Stanley Plotkin, ETATS UNIS D’AMERIQUE

Discussion : Marie-Paule Kieny, FRANCE

Vaccin candidat ChAd-COVID : Adrian Hill, ROYAUNE-UNIVaccin candidat MVA-SARS-2-S du centre allemand de recherche sur les infections :

Gerd Sutter, ALLEMAGNEComment accélérer le développement des vaccins en protégeant les volontaires

et futurs vaccins : Marco Cavaleri, FRANCE

17h0017h30

EXPERIENCE DU CONSEIL SCIENTIFIQUE FRANÇAIS COVID-19Jean-François Delfraissy, FRANCE

Conclusions

L’ACADÉMIE NATIONALE DE MÉDECINE ET LA COVID-19 : LEÇONS DE CRISE Jean François Allilaire, Secrétaire perpétuel de l’Académie nationale de médecine, FRANCE

Toutes les présentations sont en anglais

1820 - 202010

Dr. Laurent AbelHead, Laboratory of Human Genetics of Infectious Diseases INSERM - Paris Descartes University - Imagine Institute for Genetic Diseases, FRANCE

Chef, Laboratoire de génétique humaine des maladies infectieuses - INSERM - Université Paris Descartes - Institut Imagine pour les maladies génétiques, FRANCE

Pr. Moulay Hicham AfifProfessor of pulmonology at the Faculty of Medicine and Pharmacy of Casablanca - Director of Ibn Rochd University Hospital Center in Casablanca - Head of pulmonology department at Ibn Rochd University Hospital Center - President of Moroccan society of Respiratory Diseases - President of Moroccan univerity college of pulmonology - Member of scientific advisory committee of national program for prevention and control of influenza and acute respiratory infections, Ministry of Health - Faculty of Medicine and Pharmacy, Hassan II University & Ibn Rochd University Hospital Center, Casablanca - Ibn Rochd University Hospital Center, Casablanca, Faculty of Medicine and Pharmacy, Hassan II University & Ibn Rochd University Hospital Center, Casablanca, MOROCCO

Professeur de pneumologie à la Faculté de Médecine et de Pharmacie de Casablanca - Directeur du Centre Hospitalier Universitaire Ibn Rochd de Casablanca - Chef du service de pneumologie au Centre Hospitalier Universitaire Ibn Rochd - Président de la Société marocaine des maladies respiratoires - Président du Collège universitaire marocain de pneumologie - Membre du comité consultatif scientifique du programme national de prévention et de contrôle de la grippe et des infections respiratoires aiguës, Ministère de la santé - Faculté de médecine et de pharmacie, Université Hassan II et Centre hospitalier universitaire Ibn Rochd, Casablanca, MAROC

Dr. Avelin F. Aghokeng Virologist – Joint Research Unit MIVEGEC - Department of Virology - Research Institute for Development and University of Montpellier, France - Director of CDC Virology Laboratory - Centers for Disease Control and Prevention (CDC) - U.S. President’s Emergency Plan for AIDS Relief Global AIDS Program (GAP), Abidjan, Côte d’Ivoire - Institute for research and development (IRD), Montpellier, France - Coordinator of the “HIV DRUG RESISTANCE IN SOUTH” Group at ANRS France - Expert Member of the WHO HIVResNet Laboratory Working Group for surveillance of HIV Drug Resistance, Member of the ANRS Scientific Expert Panel - Virology Laboratory, Yaoundé, CAMEROUN- International center of medical research of Franceville, GABON

Virologue - Unité mixte de recherche MIVEGEC - Département de virologie - Institut de recherche pour le développement et Université de Montpellier, France - Directeur du Laboratoire de virologie du CDC - Centres de contrôle et de prévention des maladies - Plan d’urgence du président américain pour la lutte contre le sida - Programme mondial de lutte contre le sida (GAP), Abidjan, Côte d’Ivoire - Institut de recherche et développement (IRD), Montpellier, France - Coordinateur du groupe «HIV DRUG RESISTANCE IN SOUTH» à l’ANRS - France - Membre expert du groupe de travail OMS HIVResNet Laboratory Working Surveillance de la résistance aux médicaments anti-VIH, membre du groupe d’experts scientifiques de l’ANRS - Laboratoire de virologie, Yaoundé, CAMEROUN - Centre international de recherche médicale de Franceville, GABON

Liste des orateurs(par ordre alphabétique)

List of speakers(in alphabetical order)

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Pr Jean François Allilaire Permanent executive officer of French Academy of medicine, FRANCE

Secrétaire perpétuel de l’ Académie nationale de médecine, FRANCE

Pr. Christian Boitard Member of the National Academy of Medicine - Professor of Clinical Immunology - Université de Paris - Director, Institute Physiopathology, Metabolism, Nutrition (AVIESAN), FRANCE

Membre correspondant de l’Académie Nationale de Médecine - Professeur d’Immunologie Clinique, Université de Paris - Directeur de l’Institut Thématique Multi-Organismes Physiopathologie, Métabolisme, Nutrition (AVIESAN), FRANCE

Dr. Marco CavaleriHead of Biological Health Threats and Vaccines Strategy - European Medicines Agency, FRANCE

Chef de la stratégie sur les menaces et les vaccins pour la santé biologique - Agence européenne des médicaments - FRANCE

Pr. Patrice DebréProfessor emeritus of Immunology, Sorbonne University and Department of Immunology Pitié Salpêtrière Hospital , Former Ambassador for HIV/AIDS and communicable diseases, Chair of the International Relationship Committee , French National Academy of Medicine, FRANCE

Professeur émérite d’Immunologie , Sorbonne Université et Département d’Immunologie Hôpital Pitié Salpêtrière , Ancien Ambassadeur pour le VIH/Sida et les maladies transmissibles , Président du Comité des Relations internationales, Académie Nationale de Médecine, FRANCE

Pr. Carlos Del RioDistinguished Professor of Medicine (Infectious Diseases) - Emory University School of Medicine Professor of Epidemiology and Global Health - Emory Rollins School of Public Health - Foreign Secretary, US National Academy of Medicine, USA

Professeur émérite de médecine (maladies infectieuses) - École de médecine de l’Université Emory - Professeur d’épidémiologie et de santé mondiale - École de santé publique Emory Rollins Secrétaire aux affaires étrangères, Académie nationale de médecine des Etats-Unis, USA

Pr. Jean-François DelfraissyDoctor and professor of medicine, specializing in immunology.Chairman of the National Ethics Advisory Committee in 2016. Chairman of the Covid-19 Scientific Council to advise the French government in the fight against the covid-19 pandemic, FRANCE

Médecin et professeur de médecine, spécialisé dans l’immunologie.Président du Comité consultatif national d’éthique en 2016. Président du Conseil scientifique Covid-19 pour conseiller le gouvernement français dans la lutte contre la pandémie de covid-19, FRANCE

1820 - 202012

Pr. Detlev Ganten Specialist in pharmacology and molecular medicine. Founder of the World Health Summit in 2009. Chairman of the Foundation Board of the Charité Foundation. Editor of the Journal of Molecular Medicine, Chairman of the Board of Trustees of the Max Planck Institute of Colloids and Interfaces and Max Planck Institute of Molecular Plant Physiology as well as Chairman of the Board of Trustees of the Ethnological Museum Dahlem of the Prussian Cultural Heritage Foundation, GERMANY

Spécialiste de la pharmacologie et de la médecine moléculaire - Fondateur du World Health Summit en 2009 - Président du conseil de la Charité Foundation - Rédacteur en chef du Journal of Molecular Medicine Président du conseil d’administration de l’Institut Max Planck des colloïdes Président du conseil d’administration du Ethnological Museum Dahlem de la Prussian Cultural Heritage Foundation – ALLEMAGNE

Pr. Johan Giesecke Professor emeritus - Karolinska Institute, Stockholm, SWEDEN

Professeur honoraire - Institut Karolinska, Stockholm, SUÈDE

Pr. Adrian HillDirector, The Jenner Institute - University of Oxford, UK

Directeur de l’Institut Jenner - Université d’Oxford, UK

Pr. Didier HoussinPresident of the Covid-19 Emergency Committee of the World Health Organization - Full member of the French Academy of Medicine, FRANCE

Président du Comité d’urgence Covid-19 de l’Organisation mondiale de la santé - Membre titulaire de l’Académie nationale de médecine, FRANCE

Pr. Esper G. Kallas Full Professor - Department of Infecious and Parasitic Diseases - School of Medicine - University of Sao Paulo, BRAZIL

Professeur titulaire - Département des maladies infectieuses et parasitaires - Ecole de Médecine - Université de Sao Paulo, BRESIL

Dr. Carole JabetScientific Director - Quebec Health Research Fund - Montreal (Quebec), CANADA

Directrice Scientifique - Fonds de recherche du Québec Santé - Montréal (Québec), CANADA

13

Pr. Vincent JarlierBacteriologist and specialist in hospital hygiene - Pitié Salpêtrière University Hospitals - Director of the National Reference Center for Mycobacteria and Mycobacterial Resistance to Tuberculosis (CNR-MyRMA) - Member of the National Academy of Medicine, FRANCE

Bactériologiste et spécialiste en hygiène hospitalière - Hôpitaux Universitaires Pitié Salpêtrière Directeur du Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA) - Membre de l’Académie nationale de médecine, FRANCE

Pr. Marie-Paule KienyDirector - Priority Research Programme on Antimicrobial resistance, Inserm, FRANCE

Directeur - Programme de recherche prioritaire sur la résistance aux antimicrobiens - Inserm, FRANCE

Pr. Jean-François MatteiPresident of the French Academy of Medicine - Former Minister of Health, FRANCE

Président de l’Académie nationale de médecine de France - Ancien ministre de la santé, FRANCE

Dr. Brian McCloskeyCBE, MD, FFPHM, Senior Consulting Fellow, Centre on Global Health Security, The Royal Institute of International Affairs (Chatham House), UNITED KINGDOM

CBE, MD, FFPHM, Chercheur-conseil principal, Centre sur la sécurité sanitaire mondiale, L’Institut royal des affaires internationales (Chatham House), ROYAUME-UNI

Pr. Dror MevorachFull professor and the former vice dean for teaching at the medical school of the hebrew university, Head of Rheumatology research center, and chairman of medicine at the Hadassah-Hebrew University medical center, ISRAËL

Professeur titulaire et ancien vice-doyen pour l’enseignement à la faculté de médecine de l’université hébraïque, chef du centre de recherche en rhumatologie et président de la médecine au centre médical de l’université Hadassah-Hébreu, ISRAËL

1820 - 202014

Pr. Arnold MigusFormer CEO of the National Center for Scientific Research - (CNRS), Honorary judge at the Court of Audit, FRANCE

Ancien directeur général du Centre national de la Recherche scientifique (CNRS) - Conseiller

maître (honoraire) à la Cour des comptes, FRANCE

Pr. Patrick NetterMember of the National Academy of Medicine - Emeritus Professor of Pharmacology - Honorary Dean of the - Faculty of Medicine of Nancy - Former Director of the Institute of Biological Sciences of the National Center for Scientific Research - (CNRS), FRANCE

Membre de l’Académie nationale de médecine - Professeur émérite de Pharmacologie - Doyen honoraire de la faculté de Médecine de Nancy - Ancien Directeur de l’Institut des Sciences Biologiques du Centre National de la Recherche Scientifique (CNRS), FRANCE

Pr. Guang Ning Head of Shanghai Clinical Center for Endochrine and Metabolic Disease, Director and Professor of Department of Endocrine and Metabolism in Ruijin Hospital, Director of Shanghai Institute for Endocrinology and Metabolism, Vice President of Ruijin Hospital affiliated Shanghai JiaoTong University School of Medicine, CHINA

Chef du centre clinique de Shanghai pour l’endochrine et les maladies métaboliques, directeur et professeur du département d’endocrinologie et de métabolisme de l’hôpital de Ruijin, directeur de l’Institut de Shanghai d’endocrinologie et de métabolisme, vice-président de l’hôpital de Ruijin affilié à l’école de médecine de l’Université JiaoTong de Shanghai, CHINE

Pr. Stanley PlotkinEmeritus Professor of Pediatrics, University of Pennsylvania, USA

Professeur émérite de pédiatrie, Université de Pennsylvanie, USA

Pr. Angelo RavelliProfessor of Pediatrics and Director of Pediatric Residency Program, University of Genoa - Head, Division of Rheumatology, Giannina Gaslini Institute - EULAR Center of Excellence in Rheumatology 2018-2023 - Treasurer, Pediatric Rheumatology European Association (PRES) - Chair, EULAR Standing Committee for Pediatric Rheumatology - Chairman, Italian Pediatric Rheumatology Study Group, ITALY

Professeur de pédiatrie et directeur de programme en pédiatrie, Université de Gênes, Italie - Chef, Division de rhumatologie, Institut Giannina Gaslini - Centre d’excellence EULAR en rhumatologie 2018-2023 - Trésorier, Association européenne de rhumatologie pédiatrique (PRES) - Président, Comité permanent EULAR de rhumatologie pédiatrique - Président, Groupe d’étude italien sur la rhumatologie pédiatrique, ITALIE

15

Pr. Gerd SutterChair of Virology - Director, Department of Veterinary Sciences - Institute for Infectious Diseases and Zoonoses - Ludwig-Maximilians-Universität München, GERMANY

Chaire de virologie - Directeur, Département des sciences vétérinaires - Institut des maladies

infectieuses et des zoonoses - Ludwig-Maximilians-Universität München, ALLEMAGNE

Pr. Yazdan Yazdanpanah Director of the Institute of Immunology, Inflammation, Infectiology and Microbiology at Inserm and Head of the Department of Infectious Diseases at Bichat Hospital, FRANCE

Directeur de l’Institut d’immunologie, inflammation, infectiologie et microbiologie à l’Inserm et chef de service des maladies infectieuses à l’hôpital Bichat, FRANCE

1820 - 202016

Présentations des orateursCREATION OF THE FRENCH ACADEMY OF MEDICINE

AND THE CHALLENGE OF EPIDEMICS IN HISTORY

Pr. Patrice Debré

Highlights on the establishment of the French National Academy of Medicine

The French National Academy of Medicine December 20th (1820)

History of the French National Academy of Medicine

• Strengths and Dissents : Practice surveillance and governance » among surgeons (barbers) and clinicians » among Medical Faculties and their Associations

• Between physicians and the political power• From the French History: since Louis XIV (Molière) until the year of 1820.

• The Royal Academy of Medicine instead of Academy of Medical Sciences “our intention being to give as soon as possible regulation....’, abolishing malpractice of Medicine in different fields” 3 sections : Medicine (70 members), Surgery (45 members), Pharmacy (25 members) and 80 associated members, 30 members from other scientific field, 30 international members

• One Chair person (President) chosen every year • Politics (too much politics quarrels)Education (faculty members disagreement) Science

(Scientific best practice): form a consensus decision by voting, for instance the role of microbes in the epidemics outbreak

• On March18th (1707), the first official document dedicated to public health was reported: » Only the Medical Faculties (Masters) supervise physicians » Anatomy teaching in the first years of medical school » One day a week clinic dedicated to deprived population

• (1776) the Royal Society of Medicine was established - the European monarchies ruled medical practice

• (1793) from Danton’s execution to Robespierre power - Faculties and the Royal Society were abolished

• (1803) Empire of Napoleon I » several Medical Schools under Imperial governance » the Medical Society working to control epidemics » the law (May 10th) (Cabanis, Chaptal)

- Compulsory need of a diploma for medical practice - Drugs regulation and license by regulatory authorities - Internship

• (1814-1820) Contradictory influences » Surgeons aimed at independent leadership (and recovered real status) » The First Royal Physician (Portal) , and the First Royal Surgeon (Père Élysée) disputing around Louis XVIII

17

Epidemics history overview

1) Host-pathogen interactions: ...about Pasteur’s microbial theory and the link between fermentation and contagion...A debate at the ANM

• Sammelweiss and asepsis, Lister and antisepsis... but a strong skepticism towards the infectious role of microbes (Broussais: ...fallacious theories on the causes of epidemics and infections contributed to the perpetuation of dangerous illusions...a microbe is by no means necessary to the propagation of Cholera)

• A chemist among physicians, (1873) March 23rd Molecular asymmetry « life is a function of asymmetry or its consequence »

Fermentation > asymmetry > the ferments act as living organisms • First experimental evidence that a microbe (anthrax bacteria) could cause a disease: by

diluting a drop of infected blood in culture broth within a period of time, sufficient for the germ to reproduce

1) Host-pathogen interactions: ... about Pasteur’s microbial theory... The Colin debate at the ANM• Pasteur claimed that chicken are resistant to anthrax. Gabriel Colin opposed to Pasteur theory,

but could not prove it. On March19th (1878) Pasteur joined the Academy wearing a frock coat with his stovepipe hat and carrying 3 chickens in a cage.

> asymptomatic versus symptomatic cases • Anthrax : What could be the source of contagion? How could anthrax bacteria come from a

dead animal buried deep in the ground? The discovery of soil ribbons piled up by earth worms was the answer

• Reservoirs and vectors

1) Host-pathogen interactions: ...From Pasteur’s microbial theory to Covid 19 • many microbes seem to give rise in their culturing medium to substances apt to harm their own

development• Pasteur did not discover vaccination but experimental vaccines (germ attenuated with air,

heat, oxygen , age ) » chicken cholera, anthrax , swine fiver, erysipelas, and rabies

...” if a microscopic organism were to enter one or the other of the thousands species of creation, it could invade it and make it sick, its virulence will be reinforced by successive passages. I feel very inclined to believe that this is how smallpox, syphilis, yellow fever etc. appeared throughout the ages, and that it is also by phenomena of this kind that certain epidemics appear from time to time... Louis Pasteur

2) Quaratine as containment ancestor • From Leprosy to Plague: (Leprosy: a court legal statement to isolate the patient ) and Plague

(a security decision based on statistics to change the population behaviour) > First establishment of the concept: (1377) Dubrovnik, Mercado island > one month

• (1423) Venice (by laws) it was increased to 40 days, Santa Maria de Nazareth > Lazareth, Patent: the first medical administrative document for secure distance exchanges, by stretching the reach through a ladder.

• Diffusion to all Mediterranean harbors (Livorno, Napoli, Marseille...) • Inland similar decision > each city had its own policy to restrict entry, patients isolation,

communication about infected sites, “ flee quickly, long, come back late” > from Louis XIV, a national policy by the parliament and sanitary walls

1820 - 202018

2) Quaratine as containment ancestor • There were conflicts between pro (containment measures) and against (human rights, trading,

containment increased air poisoning, exposure and contagion) • Diplomacy: there was no harmonization procedures until 1876 (Yellow fever, Cholera, Plague

> quarantine)• Mary Mallon known as Mary Typhoid (1915) was isolated for 40 years under suspicious of being

asymptomatic carrier of Typhoid fever • In 1987, US authorities included AIDS to the list of contagious diseases preventing the entry into

the country. By the time, 200 HIV positive Haitians lived “isolated” at Guantanamo base, until 1993

• During SRAS outbreak (2003) Suspected cases were forced to containment by the police officers.

Emergence of emergence

The causes through the ages: ...from Louis Pasteur until Covid19 outbreak

Emergence and spread of Covid19

• Plutarque (year 100 AC), Table speech > Philon and Diogenos• Joshua Lederberg (1990)Reports on emergence : Complex dynamic due to Microbial

Darwinism and the behavior of our societies

• Wildlife and Farming (Nipah virus, H5N1, H1N1, Lyme Disease), bushmeat (SRAS, Covid19) • Demography, Society behavior (HIV, Syphilis, Tuberculosis, Pertussis)• Population displacement, Migrations (chikungunya), Trade (Monkey pox, Dengue, H5N1), Air

travel (SRAS, West Nile)• Sanitary conditions, hygiene (Cholera, Staphylococcal), health system (trypanosomiasis),

foodborn diseases (E.Coli, Salmonella) • Pathogen evolution (AMR), Climate Changes (Rift Valley fever, West Nile fever)

• Wildlife and bushmeat (Wuhan). Population displacement (air travel). By the Chinese New Year, WHO declared the Pandemy, virus mutations all over the world and Emergent Diseases:

1- SARS-CoV2 (Covid19) > aged and vulnerable2- Children were not spared > emergent SARS-CoV2 Kawasaki-syndrome Again, sanitary measures under debate:

• Social distance, masks, lock in, lock down, quarantine, country borders • (Sammelweiss) washing hands and surface cleaning• (Pasteur) >110 vaccine projects ongoing, no anti-viral proven effective• Practice: The ill saved by Oxigen, Environment: the planet breathing, Behavior: life through the

computer screen

19

Covid19 global burden

1820 - 202020

PUBLIC POLICIES AND STRATEGIES AGAINST SARS-CoV-2 Chairmen : Patrick Netter, Arnold Migus, FRANCE

2005-2009 - H5N1 threat and WHO alert led to a high degree of preparedness in France : Overall planning; business continuity; « white plans » for massive surge of patients in hospital ; logistics and stockpiling ( masks, antivirals, vaccines); exercises; european coordination (HSC);

2009-2011- H1N1 pandemic acted as a trap for preparedness: Too much reaction ; too much preparedness; too much expenses;

2012-2020 - MERS CoV and Ebola were not enough as wake-up calls. Intensity in preparedness declined ( a marker: National State stockpile of masks: nearly 2 billions in 2009; around 100 millions in 2020).

JANUARY, THE 30th, 2020When WHO declared that Covid-19 was a public health emergency of international concern, the degree of preparedness in France was low:

• No vaccine; no demonstrated effective antivirals; a penury of masks; a limited capacity for PCR testing; little anticipation in clinical research studies;

• The Govt. had to use the 2011 pandemic plan as a reference document for crisis management, with two « innovations »: two scientific councils in addition to existing expert institutions; two crisis centres;

• A transition in political leadership at the Ministry of Health.

MARCH, THE 17th, 2020A lockdown-based management policy inspired by two previous experiences :

• The efficacy of social distancing in China (February 2020); • To some extent, the efficacy of social distancing in Italy (March 2020).

A management policy facilitated by two series of events:• The initial limitation of virus transmission to the northeastern part of France;• The capacity of hospitals to hold on, thanks also to the transfer of some severe patients in other

French regions and in Germany.

APRIL 2020A true preparedness phase for lockdown easing :

• Little by little, a « gathering » of the scientific expertise of the Comité scientifique, the Haut Conseil de la santé publique and Santé publique France, well-supported by epidemiological modelization team;

• A cross-government multidisciplinary team attached to the Prime Minister and dedicated to preparing lockdown easing;

• A phased lockdown easing.

FROM MAY THE 11THPreparedness allowed phase 1 of lockdown easing to start based upon :

• Epidemiological criteria and modelization studies;• Viral transmission intensity-based territorial distinctions;

Pr. Didier HoussinThe forgotten preparedness strategy

21

• Improved access to all sorts of masks ;• Improved capacity for PCR tests;• Dedicated policy for screening of patients and contact tracing mainly based upon GPs, the

health insurance system and regional health agencies.The key word of this phase was progressivity. Reconciliation between mitigating transmission and some recovery of economical and social activities was the most difficult aspect. Obligation to wear a mask in collective transportation systems: a key decision, considering the difficulty to keep 1 m. distance between people.

FROM JUNE THE 2NDPreparedness allowed phase 2 of lockdown easing to start based upon :

• Continuing improvement of the epicurve • Encouraging results with patients screening, contact tracing and PCR tests;• Its main features were :• Increased access to schools .• Suppression of the 100 km limitation of travel within France;• Cautious opening of bars and restaurants.

A perspective was delineated for a phase 3 of lockdown easing starting on June the 22nd and covering the summer holidays period.Unification of crisis centres into a single centre led to conclude the preparedness role of the multidisciplinary cross-government team.

AT THIS STAGE, JUNE THE 16THLockdown easing did not lead to a rebound of the epicurve.

• Screening led to the identification of 210 clusters since May the 11th, but none of which appeared critical;

• Sero-epidemiological studies are ongoing which should allow to better assess the risk of a second wave;

• Access to overseas territories and international air travel remain significant obstacles to overcome ;

• Scenarios for iterative lockdown are prepared in case of a marked rebound of the epidemics.

PERSPECTIVES ABOUT FRANCE • Significant time will certainly soon be devoted to parliamentary and judiciary inquiries.• Then, initiatives will probably be taken to improve preparedness at national level with regard

to emerging pandemic viruses. For how long?• National decisions will be influenced by the final diagnosis : was it worse to have the epidemics

run on to herd immunity ? Or was it worse to have the social, economical and health consequences of several weeks of lockdown ?

• At EU level, will France support a reinforcement of the Union competences concerning health security, in order to better anticipate and generate more coherent responses ?

• Internationally, France supported an initiative to suspend debt to help Africa deal with coronavirus and the independent evaluation which was decided at the last World Health Assembly. It probably will support the role of WHO.

1820 - 202022

Pr. Moulay Hicham AfifResponse Strategy and Epidemiological Situation in Morocco

Area : 710.850 km2

Population : 35.930.614Density : 50.5 h/km2

Official Languages : Arab & Amazigh

Objectives of the strategy Axes of intervention

Objectives of the strategy and Axes of interventionThe national response strategy of the coronavirus pandemic is based essentially on :

• High directives of His Majesty King MOHAMMED VI, may God Assist Him, involving and mobilizing all sectors to counter the pandemic and mitigate its impact on the economy

• Anticipation in the response (experiences of countries previously affected by Covid-19)• Earliness in Testing, Treating and Tracing• Aligning the dynamic of response to the dynamic of evolution

Immediate response strategy based on proactive measures

March 2nd : First imported caseBased on Royal Directives, series of measures are adopted to contain the epidemic spread :

• Between March 10th and 15th : Temporary suspension of air flights and shipping lines• From March 16th : Suspension of courses in schools and universities and keeping on remote

courses• March 16th : Temporary closure of public places• March 20th : Declaration of a state of emergency and extending it twice (until June 10th) and

a ban to citizen’s movement without authorities authorization, except for persons working in vital sectors

• March 21st : Prohibition of traveling inside the country and suspension of railway lines• Royal pardon for the benefit of 5654 inmates to prevent the spread of the virus in prisons• April 7th : Obligation to wear Masks (price fixing and availability of sufficient quantities)

1 Preventing the introduction of SARS-CoV-2 on national territory

2 Detect cases early and contain the spread

3 Organize a national response adapted to local health system

4 Strengthen infection prevention and control measures in health care settings

Monitoring and

surveillance

Preparation of the

medical system and

disease control

Information and

communication

Governance and

coordination

23

Governance and coordination

• Steering of the strategy on central and regional levels: Interministerial Coordination Committee, Central Command Post / Regional

• Institutionalization of the National Scientific and Technical Committee for the Control of Acute Respiratory Infections. Elaboration of this committee are highly involved in the Covid-19 treatments recommandation

• Publication of ministerial circulars standardizing the medical care of Covid-19 cases: » Case definition and management of Covid-19 patients: Possible cases, confirmed cases, close contacts....

» Therapeutic protocol: Chloroquine - Azithromycin ... (March 23rd) » Management of severe and critical cases in intensive care, children and pregnant women

Preparation of medical system

• 72 hospitals (public, foundation and private): » 13.456 conventional hospital beds for mild and moderate cases » 1.718 intensive care beds

• Setting up temporary hospitals (Casablanca-Settat region: 1080 beds…)• Providing hotel facilities for contact cases not able to be on self-confinement and for care staff• Enlarging of the national platform of laboratories (20 public, 3 private and 5 military laboratories)

Local production of protective devices: • Production of more than 10 million masks/day• Increasing production of existing units• Orientation of the activity of textile companies

Legal arsenal : Texts of laws for pandemic management, public expenditure management, state of health emergency, creation of the Covid-19 Special Fund

Creation of a special fund dedicated to the management of the pandemic:• Coverage of expenses for upgrading

the medical device

• Supporting the national economy• Preserving jobs and mitigating the

social impact of the pandemicEfficient information system:§ Identification of eligible people for financial

assistance (RAMED)§ Tracing application for positive cases and

potential contacts

Scientists' expertise : H1N1, Ebola…

Pillars of the strategy

1820 - 202024

Information and communication

• Daily public information on the epidemiological situation: » Daily press briefing » Website dedicated to Covid-19

• Permanent interaction with national public opinion on the evolution of the global and national epidemiological situation through the media

• Raising citizens’ awareness of prevention and protection measures against the risks of infection (production of capsules, reports, posters, leaflets, etc.)

• Daily interactive meetings of medical specialists to answer citizens’ questions about the epidemic (phone lines, social media, broadcasts, etc.)

• Reactivity to any information from all regions of the Kingdom and taking the necessary action

Epidemiological Situation

Situation on June 9th

Positive 8437

- Recovery 7 493 (88.8%)

- Deaths 210 (2.5%)

- Active 734

Excluded 331 134 < 12 /100 00012.0 - 21.0 /100 000More than 21/100000

41%

43%

12%

3%1%

Clinical Status

Asymptomatic Mild Moderate Severe Critical

X Active casesX DeathsX Recovery

Our country avoided:• >300 000 cases• >9 000 deaths• >7 000 ICU admissions

Therapeuticprotocol

25

Post-Containment : Strategy and Vision

Why?§Controlling the epidemic§Optimal management of other morbidities§Economic Burden of Containment

How ?

§ Progressive§ Flexible§ Adaptable

Vision§ Capitalization of pandemic management experiences

§ Scientific research and development: vaccination§ Gathering efforts for the research development § Commitment of all countries to fight the pandemic

1820 - 202026

Dr. Brian Mc Closkey

Early timeline : January - March 2020

January 31 – first 2 cases in UK (travelled from China)February 10 – 8 cases in UK (ex Singapore via ski resort)February 26/27 – outbreak at conference in EdinburghMarch 2 – first “COBRA” mtg (UK government emergency committee)March 3 UK government “action plan”March 5 – first UK death; UK moves from “containment” to “delay”March 12 – PHE stops contact tracingMarch 16 – Cases: ~1500, deaths: 55; government advises reduced travel and social contact; MGs discouragedMarch 17 – NHS prepares to wind down routine activityMarch 18 – Government announces all schools will close from March 20March 20 – Cafes, pubs and restaurants ordered to closeMarch 23 – “Lockdown” begins – social distancing, no travel

UK COVID Action Plan - March 2020

• Contain : detect early cases, follow up close contacts, and prevent the disease taking hold in this country for as long as is reasonably possible

• Delay : slow the spread in this country, if it does take hold, lowering the peak impact and pushing it away from the winter season

• Research : better understand the virus and the actions that will lessen its effect on the UK population; innovate responses including diagnostics, drugs and vaccines; use the evidence to inform the development of the most effective models of care

• Mitigate : provide the best care possible for people who become ill, support hospitals to maintain essential services and ensure ongoing support for people ill in the community to minimise the overall impact of the disease on society, public services and on the economy

Current Situation Report

27

Epicurve - to 10 June 2020

Key drivers

• Impact on NHS• Public health capacity (and utility)• Impact on children• Uncertainty• Legacy from 2009 H1N1 Pandemic ?

Key assumptions

• Mid-March:• Epidemic doubling every 5-7 days

» Hindsight: doubling every 3-4 days• Point importations, mainly from China

» Hindsight: Over 1300 importations, mainly from Europe (China-0.1%)• Children significant driver of transmission

» Hindsight: ???

Key questions

• Science and Politics » How do we “follow the science” when there is no science? » How do we support decision making without data?

• Absolute science v pragmatic science » Should scientists consider the consequences of the decisions made on their advice?

• Modelling v “shoe leather” epidemiology » Modelling is essential in the early stages of an outbreak, but it comes with its own biases and pre-conceptions

» Epidemiology may be more reliable but takes longer• What is the right weighting for “caution”?

» Decisions made “out of an abundance of caution”• How do we unmake decisions?

» Once decisions are made, particularly when the science is not definitive, it is difficult to reverse them

1820 - 202028

Pr. Detlev GantenLessons Learned from COVID-19 : Results and Development of Global Health in Germany

Time Line : Chronology of COVID-19 in Germany

16-01 Christian Drosten develops diagnostic test for SARS-CoV-2 (RT-PCR)

01-02 ~ 100 Germans return from Wuhan (quarantined); reporting duty for SARS-CoV-2 is introduced

24-02 MoH Jens Spahn declares at press conference that the epidemic has reached Europe 10-03 Crisis team at federal

gov. Recommends to cancel all meetings > 1.000 participants

16.03 First travel restrictions within the EU

18.03 Chancellor Merkel’s address to the Nation

12.03 Hospitals prepare for growing number of patients; begin of lockdown measures

11.03 WHO declares COVID-19 outbreak as a pandemic

27-01 first confirmed patient in Bavaria

27-02 Crisis team at federal gov. (Health, Interior) takes up work: first recommendation regarding intl. travel & large events; Robert Koch-Institut starts daily press briefing until beginning of May

29

Role of the Academies - Leopoldina

21-03-201. Statement

• Acute crisis

• Biomedical perspective


• Country in lockdown

• Recommendations for gradual return to public life


• Preparing for normalization

• Broader societal perspective


• Sustainable healthcare system

German Corona Consensus Dataset (GECCO)

• German Corona Consensus Dataset (GECCO) • part of the initiative of German Universities and partners : Corona Component Standards

(COCOS) > standardization and wide availability of data • Core data set of more than 80 elements on COVID-19 patients in a uniform format and standard• contains all relevant information, starting with personal data such as age, sex, height and

weight, laboratory values such as blood pressure or cholesterol levels, risk factors, medication intake, symptoms and initiated therapy

Source: https://www.aerzteblatt.de/nachrichten/113431/Einheitlicher-Datensatz-fuer-COVID-19-Forschung-entwickelt

Notification Pathways

1820 - 202030

Current Situation : Corona Infections in Germany

SWOT Analysis of the German COVID-19 Response

• The total incidence is 219 cases/100,000 inhabitants - varies greatly between the federal states.• Currently, sufficient treatment capacities are available.• 4 million laboratory tests have been recorded to date, of which approx. 5.3% have tested

positive for SARS-CoV-2. • Outbreaks in some districts with high case numbers: religious events, restaurants, asylum-

seekers’ homes, meat-processing plants

Source: https://www.sueddeutsche.de/wissen/corona-zahlen-weltweit-news-1.4844448

Estimated number of recovered

Currently infected

Deaths

STRENGTHS WEAKNESSES

THREATSOPPORTUNITIES

• Excellent science, early testing and policy advice

• Early contact restrictions

• Health infrastucture – strong outpatient sector takes pressure off hospitals

• Financial strength – to mitigate economic impact

• Federal system allows for flexibility

• Crisis communication, central part of the strategy: RKI, Government, TV, Journals

• Local public health authorities underfinanced, separate from science and universities

• Late centralized procurement and distribution of protective equipment for health workers

• Federal system creates uncertainty and leads to a political « race » for loosening restrictions

• Weak culture of controversial public discourse

• Lack of interdisciplinary and transdisciplinary discussion

• Europe: EU Council for Health, strategic coordination, drugs, equipment, funding, structures, reporting, (see SPH)

• Network of Federal and State crisis managment on standby

• Acceptance of new technologies: Apps, digitilisation, data handling, innovation culture

• Public is sceptical of tracing apps, medical data,

• Social and economic consequences of the lockdown decline of public support and compliance;

• Rise of extremist groups and conspiracy myths, vaccination deniers

• Personalisation of controversies, agression

31

Global Health Structures in Germany (Examples)

A Holistic Concept of Transformative Translation and Innovation From Bench to Bedside to Global Health (and back incl. Reverse Innovation)

German Health Alliance

German Alliance for Global Health Research

Global Health Hub Germany

German Platform for Global Health

World Health Summit

Association of health care players, especially the export-oriented health care industry

Interdisciplinary researchalliance

Broad network platform with members from different sectors

Platform of civil society organizations and initiatives

Interdisciplinary, international and intersectoral annualconference

active since 2019 active since 2020 active since 2019 active since 2011 active since 2009

Initiative of the Federation of German Industries (BDI)

Initiative and funding by the Federal Ministry of Education and Research (BMBF)

Initiative and funding by the Federal Ministry of Health (BMG)

Action alliance with self-organization (no sponsor)

Led by the M8 Alliance of Academic Health Centers, Universities and National Academies

Offices in Berlin and Bonn

Secretariat at Charité –Universitätsmedizin, Berlin

Secretariat at Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH, Berlin

Office at medicoInternational e.V., Frankfurt am Main

Permanent team at Charité –Universitätsmedizin, Berlin

gha.health/ www.globalhealth.de www.globalhealthhub.de www.plattformglobalegesundheit.de/

www.worldhealthsummit.org

1820 - 202032

World Health Summit 2020Berlin, October 25-27, 2020

Topics:• Pandemic Preparedness, Covid 19• Strengthening of the Role of the EU• The WHO – SDG 3 Action Plan (with Partners)• Digital Health• Translational Research, « Holistic Innovation »

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Pr. Johan Giesecke

Number of notified cases per week

Incidence per 100 000 by age and sex

Increase last weeks:In the middle of May, Government decided that 100 000 persons per week should be PCR tested(Swedish population ≈ 10 million)

Number of tested and confirmed per week

Cumulative incidence per 100 000 by region

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Number of deaths per week

Swedish strategy - aims

Some concrete examples

• Launched mid-March (contact intensity dropped by 70% in a week)• Achieve its aims not by laws and policing, but rather by explaining – and getting acceptance

for – the rationale for restrictions taken• Protect the old and frail with minimal disturbance of society’s functions• Flattening the curve of incidence so the healthcare system will be able to cope with the peak• Social distancing, mainly by supporting work from home• Testing all suspect patients admitted to hospital and all staff with symptoms• Extensive testing of inhabitants of care homes and their staff

• Stay at home as soon as you feel the slightest sign of infection• Physical distancing (one arm’s length)• Minimise number of contacts (especially for 70+)• No visits to care homes• Daycare and schools up to 16 yo open• Secondary schools and universities were closed (but now opened again)• Max 50 people in meetings/events• Domestic travel max 2 hrs (but free since yesterday)• Wash hands 20 times per day

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Dr. Avelin AghokengFrom coronaviruses to SARS-CoV-2

Coronaviruses

• Coronaviridae family.• Large family of Single-stranded enveloped RNA viruses.• Can be divided into four major genera.• Largely circulate in animals (mammals, birds…)

Before 2002Caused mild respiratory infections in immunocompetent humans

Coronaviruses can infect humans, first one isolated in 1965.

PATHOPHYSIOLOGY OF COVID-19Chairmen : Patrice Debré et Christian Boitard, FRANCE

Cui J et al., Nat Rev Microbiol. 2019Su S et al., Trends in Microbiology, 2016

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Human coronavirus - HCoV

Human coronaviruses (HCoV) are of animal origins.• Results of cross-species transmissions that may involve intermediate hosts.• Six HCoV were reported until recently, and included coronaviruses mostly from bats as natural

reservoir and generally involving one or multiple intermediate hosts.

• Severe, deathly infections associated with HCoV were fist reported in 2002-2003 and 2012-2018.

• SARS-CoV – Severe acute respiratory syndrome coronavirus

• MERS-CoV – Middle East respiratory syndrome coronavirus

?

Cui J et al., Nat Rev Microbiol. 2019

End 2019

Zhou P et al., Nature, 2020Zhou P et al., Curent Biology, 2020

Phylogenetic tree of the full-length virus genome

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• RmYN02 and RatG13 (Rhinolophusbats) are ≈ 95 % identical to SARS-CoV-2 at the whole genome level.

• Pangolin-CoVs are the second closest relative of SARS-CoV-2 (85.5% to 91.02% sequence similarity) at the whole-genome level.

• Pangolin-CoV (Guangdong lineage) is the closest relative of SARS-CoV-2 in the RBD (determines virus host range).

Probable Pangolin Origin of SARS-CoV-2Associated with the COVID-19 Outbreak

Zhou P et al., Nature, 2020Zhou P et al., Curent Biology, 2020Zhang T et al., Current. Biology, 2020

From : Zhang T et al, Current. Biology, 2020

SARS-CoV-2 : host-virus interactions

• Droplet-based transmission• Fomite-based transmission• Others...

Tissue tropism of SARS-CoV-2 in ex-vivo cultures of human respiratory tractFrom : Hui, K.P.Y et al., Lancet Respir Med, 2020

In the respiratory tract (but, not only) :• Bronchial epithelium - ciliated cells and non-

ciliated cells, club cells• Lung parenchyma - type 1 pneumocytes

Hui, K.P.Y. et al., Lancet Respir Med, 2020Wan Y et al., Journal of Virology, 2020Zhou P et al., Nature, 2020*Hoffman, M. et al., Cell, 2020

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• Binding of the viral spike (S) proteins to ACE2 • S protein priming by cellular protease – TMPRSS2*

Angiotensin-converting enzyme 2 (ACE2) is the cognate cellular receptor of SARS-CoV-2

Source: Wan Y et al., Journal of Virology, 2020

Source: Zhou P et al., Nature, 2020

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Bunyavanich, S. at al., JAMA, 2020Sironi, M. et al., Infection, Genetics and Evolution, 2020

Rapid spread of SARS-CoV-2 in humans

SARS-CoV-2 : ongoing outbreak

Undiagnosed cases are not there

Globally, as of June 15, 20207,761,609 confirmed ases430,241 deaths over time

Source: World Health Organization; June 15, 2020

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Genomic epidemiology of SARS-CoV-2

Global subsampling: 4725 of 4725 genomes sampled between Dec 2019 and Jun 2020.Source: https://nextstrain.org/ncov/global?c=country (accessed date: June 10, 2020)

In conclusion• SARS-CoV-2 is one of the major zoonosis of our century.• Tremendous efforts are ongoing to understand the virus/disease & solutions.• But, more attention such be paid to low-resourced regions with limited data.

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Pr. Angelo RavelliChild presentations and Kawasaki-like syndrome

Pediatric Inflammatory multisystem syndrome and SARS-CoV-2 infection in children

• Several countries affected by the COVID-19 pandemic recently reported cases of children that were hospitalised in intensive care due to a rare paediatric inflammatory multisystem syndrome (PIMS).

• The presenting sugns and symptoms are a mix of the ones of Kawasaki disease and toxic shock syndrome and are characterized, among others, by fever, abdominal pain and cardiac involvement.

• A possible temporal association with SARS-CoV-2 infection has been hypothesised because some of the children that were tested for SARS-CoV-2 infection were either positive by polymerase chain reaction (PCR) or serology.

Dong Y et al. Pediatrics, 2020

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Is it Kawasaki disease or a different illness with some similarities with Kawasaki disease?

Common clinical manifestations with KD• Fever, rash, conjunctival injection, cervical adenopathy, lip and oral changes, swollen hands

and feet, irritability

Clinical manifestations not common in KD, but frequent in PIMS-TS/MIS-C• Diarrhea, meningeal signs, myocarditis, MAS (1-2% in KD 20-30% in Kawa-COVID), toxic shock

syndrome (5-7% in KD 30-40% in Kawa-COVID)

Clinical manifestations seen in PIMS-TS/MIS-C, but not in KD• Limphopenia, relative thrombocytopenia (with the exception of MAS and TSS)

Other similarities between PIMS-TS/MIS-C and KD• The vast majority of children were given initial treatment with IVIG• Corticosteroids effective in patients with IVIG resistance or major complications (TSS or MAS)• Self-limited course• Some children developed coronary aneurysms

Main difference between PIMS-TS/MIS-C and KD• Older age in PIMS-TS/MIS-C (> 5 years versus < 5 years in KD)

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What is the pathophysiology of PIMS-TC/MIS-C ?

Mechanism ??

• Timing a month after COVID19 curve• Majority negative for SARS-Cov2 Virus but positive for Antibidoy• This suggests the illness is mediated by the development of acquired rather than by direct viral

injury

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The funnel hypothesis

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KD is not a disease, but a syndrome

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KD is not a disease, but a syndrome

Pr. Dror MevorachCharacterizations of the cytokine storm in patients with COVID-19,at Hadassah-Hebrew University Medical Center

Immunological biomarkers are particularly important, as immunopathology has been suggested as a primary driver of morbidity and mortality with COVID-19. Several

• cytokines and other immunologic parameters have been correlated with COVID-19 severity. Most notably, elevated IL-6 levels were detected in hospitalized patients, especially critically ill patients, in several studies, and are associated with ICU admission, respiratory failure, and poor prognosis (Chen et al., 2020; Huang et al.,2020; Liu et al., 2020). While there are reports that levels of IL-6 at first assessment might predict respiratory failure (Herold et al., 2020), other publications with longitudinal analyses demonstrated that IL-6 increases fairly lateduring the disease’s course, consequently compromising its prognostic value at earlier stages (Zhou et al., 2020).

• Increased IL-2R, IL-8, IL-10, and GM-CSF have been associated with disease severity as well, but studies are limited and further studies with larger cohorts of patients are needed to indicate predictive power (Gong et al., 2020;Zhou et al., 2020).

Cytokine storm characterizes other infections :• For many years, a disproportionate inflammatory response to invasive infection was considered

to be central to the pathogenesis of sepsis, but it is now clear that the host response is disturbed in a much more complex way, involving both sustained excessive inflammation and immune suppression, and a vfailure to return to normal homeostasis.

Tom van der Poll et al. Nature Reviews Immunology (2017).

Chimeric Antigen Receptor (CAR) T Cells Engrafting, Trafficking to Tumor, and Proliferating Extensively after Infusion may cause Cytokine Release Syndrome

June & Sadelain. Chimeric Antigen Receptor Therapy. N EnglJ Med 2018.

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What are the characterizations of cytokine storm associated with COVID19 ?

Covid-19: Cytokine/chemokine stormThe following diagram (Santo Dellegrottaglie, Cardililogo, Napoli) illustrates suggested understanding of the pathophysiology of COVID19.

Methods

• Over 100 patients were hospitalized at Hadassah-Hebrew University Hospital, Jerusalem, in the recent 3 months with the diagnosis of COVID19. We summarized the clinical outcomes and their correlation to a cytokine storm at Hadassah.

• 40 different cytokines/chemokines/ Hematopoietic Growth Factoprswere analyzed and compared to clinical manifestations.

• Luminex® Cytokine/ Chemokine analysis. Serum cytokine/chemokine measurement was performed using the Luminex MAGPIX system (Luminex Corp, Texas, USA) and analyzed with Milliplexanalysis software (MilliporeMA, USA).

• ELISA analysis. The following cytokine/ chemokines were measured by sandwich ELISA kits: IL-18 (R&D), MCP-3 (R&D), TNFR1 (R&D), TREM-1 (R&D), procalcitonin (PCT) (IBL-America, MN, USA).

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Acute phase markers, hematological and clinical features of COVID-19 patients

Pro-inflammatory cytokines in COVID-19 patients

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Anti-inflammatory cytokines in COVID-19 patients

Chemokines in COVID-19 patients

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Spearman’s correlation matrixof intermediate COVID-19 patients

Summary

• Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome.

• Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and suggested elevated cytokines/chemokines included IL-6, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-3, and IL-1ra.

• COVID-19 is characterized by fundamentally an exaggerated inflammatory disease mediated by the activation of the innate immune/adaptive system, that partially correlates to disease severity and may harm lungs and the different organs and lead to organ failure and high mortality rates.

• Specific characterizations of the immune response may shed light on pathophysiology and possible therapeutic targets.

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Pr. Yazdan YazdanpanahThe French strategy

COVID-19 AND THERAPEUTIC TRIALS Chairmen : Yves Buisson et Vincent Jarlier, FRANCE

Therapeutic drug candidates

Remdesivir Lopinavir/ritonavirInterferon (IFN)-ß 1a

Hydroxychloroquine

REsearch and ACTion, targeting emergING infectious diseases

Multi-centre, adaptive, randomized trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults (v3.0, March 3, 2020)

Sponsor INSERM – European trialMarch 22, 2020: First inclusion in France

WHO international trial (v10.0, March 22, 2020)March 29, 2020: Signed agreement between DisCoVeRy and Solidarity

Repurposing drugs

TMIN

G

Solidarity

PI: Pr F.AderMethodologist: Pr F.Mentré

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Patient hospitalized with COVID-19 in need

of oxygen support (conventional unit or Intensive Care Unit)

Standard of care (SoC)

SoC +Remdesivir IV

200 mg day 1 then 100 mg for 9 days

SoC +Lopinavir/ritonavir PO

400/100 mg BID for 14 days

SoC +Lopinavir/ritonavir PO

400/100 mg BID for 14 days+ IFN-ß-1a SC

44µg at day 1, day 3, day 6

SoC +Hydroxychloroquine PO

400 mg BID day 1 (600 mg BID if nasogastric tube)then 400 mg QD for 9 days

Randomization

Study design summary

Phase III, therapeutic intervention, 36 months

Prospective adaptive, randomized, open, controlled trial

Multi-centre

Adults ≥ 18 years, hospitalized for COVID-19

Randomly allocation will be stratified by:• Region of inclusion,• Severity of illness at enrolment:

» Severe disease: Patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO;

» Moderate disease: Patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO

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Day 15 : primary end-point

Other endpoints

The primary endpoint is the subject clinical status on a 7-point ordinal scale at Day 15

Not hospitalized participants who answer YES (NO) to the question“Are you able to carry out all the activities, including physical activities, that you carried out before the first symptoms of COVID-19?” will have a score of 1 (2).

The scale is as follows :1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities;3. Hospitalized, not requiring supplemental oxygen;4. Hospitalized, requiring supplemental oxygen;5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;6. Hospitalized, on invasive mechanical ventilation or ECMO;7. Death.

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Inclusion curves until June 2 : 754 patients

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Link between DisCoVeRy and Solidarity

DisCoVeRy is a daughter trial (add-on trial) of SolidarityData of participants included in DisCoVeRy to be sent to the Solidarity database

• Baseline Patient details • Three endpoints to be analysed only by the WHO Solidarity DSMC

» in hospital death » time to ventilation » duration of hospitalisation

• More than 4000 patients enrolled

• Currently 500 patients enrolled per week

An experimental model of non-human primates infected with SARS-CoV-2 that reproduce human infection

Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non-human primates

Findings do not support the use of HCQ, alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.

Maisonnasse et al Nature 2020 (in press)

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COVID-19 natural history (cohort of patients)

Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Oberfeld et al, Cell, 2020

Lescure FX Lancet Infect Dis 2020

French COVID; > 3000 patients with clinical, virological, PKPD dataUp to 6 months of follow-ip

• 21 patients with pneumonia on O2, including 2 on mechanical ventilation• TCZ: 400 mg once• 19/21 improved and were discharged

Xu et al. chinaXiv:202003.00026v1. 16 March 2020

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CORIMUNO-19: Cohort multiple randomized controlled trials of immune modulatory drugs and other treatments in COVID-19 patients

Treatment Proposal

Key features :1. Recruitment of a large observational cohort of patients with the condition of interest2. Regular measurement of outcomes for the whole cohort3. Capacity for multiple randomised controlled trials over time within this cohort

» Testing different interventions » Frequent interim monitoring using a Bayesian approach » Exploratory trials; not for registration

One crucial feature of CORIMUNO-19 trials is to remain as flexible as possible, in an urgency context, when information may change quickly. The study therefore attempts to maximize information from limited data generated, while allowing rapid decision

Biotherapy anti Cytokine » Anti IL6R (Sarilumab, Tocilizumab) » Ati IL6R + Hydoxychloroquine+Azythromycin) » Anti IL-1 (soluble receptor, Anakinra, Canakinumab) (Group 1 and 2) » Anti IL-17 (Sekukinumab) » Anti TNF » Dexamethasone++

Kinase Inhibitor (group 1 only) » Baricitrinib (JAK1, JAK2 + Antiviral activity) » Fedratinib (JAK2, antiviral activity) » Ruxolitinib ?(JAK1, JAK2, no Antiviral activity) » Masitinib+ Isoquercitin (KIT, Lyn, Fyn +antiviral activity + Antioxydant)

Complement Inhibition (Group 1 and 2) » Eculizumab (C5a inhibition) » Zilucoplan (C5 peptide inhibitor)

PI: Olivier HermineMethodological and statistical group : Philippe Ravaud, Raphael Porcher, Mathieu Resche-Rigon

Plasma therapyDay 28 post infection plasmaIgIV Echanges plasmatiquesRituximab ++

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Population and primary endpoint

The on-going trials in corimuno

CORIMUNO-19 Cohort inclusion: Age ≥ 18, hospitalized with laboratory-confirmed SARS-CoV-2 infection, with symptoms

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COVID-19 natural history

Antivirals(test and treat)

Map of the registered clinical trials (Anticovid platform for COVID-19 on 26 April 2020).

Antivirals + immune modulatory drugs

A better regulation of clinical trials

Peiffer-Smadja et al. J Antimicrobiol Chem 2020

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From Repurposing drugs to

Novel small molecule therapeutic & neutralising monoclonal antibodies candidates against the current SARS-CoV-2

H2020 EU-RESPONSE proposal

CARE - Corona Accelerated R&D in Europe (Y Levy; IMI 2020)

Title of Proposal: European Research and Preparedness Network for Pandemics and Emerging Infectious Diseases (EU-RESPONSE)

Duration: 5 yearsPartnership: 21 partners from FR, NO, IT, PT, SK, BE, HU, IE, CH, TR, LU, AT, ES, GR, PL, CZ

Overall aim: build a multinational, adaptive pan-European COVID-19 and emerging infectious diseases platform trial network, based on existing initiatives, experiences and competencies. Although in the short-term this project will focus on COVID-19, the mid-term/long-term objectives are to build a platform trial network on emerging infectious diseases in general.

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Dr. Carole JabetCOVID-19 & clinical trial - Quebec’s key features

FRQS mission

Support and promote excellence in research and training for the next generation of health professionals in order to stimulate knowledge development and innovation

FRQ and COVID-19 - Science is on all agendas

• Chief Scientific Officer – Pr Rémi Quirion » To advise the government on any matters pertaining to the COVID-19 crisis » To promote federal and international partnerships on various COVID-19 topics » To inform the general public and reinforce the importance of the scientific approach to manage the crisis

• Implementation and funding of structuring initiatives » COVID-19 Quebec biobank – 10 000 participants www.bqc19.ca » Quebec Network for COVD19 and pandemic

FRQS and COVID-19 - Importance of the continuum science research - innovation

• Mobilization of the scientific and innovation community through a large call to solutions » > 750 proposals ; selection by Ministry of economic development; Ministry of Health and FRQ

• Support to several major vaccine development projects

• Development of evidence for better management of the overall health of the population, including social aspects

CanCOVID : a network to expedite communication and collaboration between the scientific, healthcare and policy communities

Clinical research in a context of pandemic - Key bodys to provide guidelines

HEALTH CANADA• Health Canada is prioritizing the review of all COVID-19 related clinical trial applications and

has already authorized a number of trials.• interim order for clinical trials for medical devices and drugs related to COVID-19, to streamline

the investigation of potential therapies and facilitate broader access for Canadians to COVID-19 related investigational drugs and medical devices

Institut national d’excellence en santé et en service sociaux (INESSS)• Publication of the guideline : Access to promising products and interventions in the context of

pandemic: a rigorous and informed choice

FRQS • Special Advisory Committee for clinical trials in a context of pandemic• 6 key opinion leaders• Ministry of Health, INESSS, FRQS

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Guiding principles communicated to healthcare institutions

Clinical Trials registers In Quebec and Canada

MANDATE OF THE FRQS ADVISORY COMMITTEEEnable informed decision-making and concerted efforts by institutions, research teams and healthcare professionals regarding the conduct of research projects, taking into account (1) adjustments in the care of patients made necessary by the pandemic / COVID AND (2) collective responsibility to accelerate (a) the acquisition of evidence-based data and knowledge through a scientific / ethical approach and (b) integrating this knowledge urgently, efficiently and safely in the care and follow-up of patients with COVID or prevention at the provincial level.

CANADA• 39 authorized clinical trials• Vast majority of investigator-initiated trials; mainly hospitals; ONTARIO - QUEBEC• 12 led by biotech or pharma companies

QUEBEC• 11 RCT• > 70% are conducted at the national or international level

GUIDING PRINCIPLESImportance and impact of the proposed clinical research project, in the context of the pandemicExhaustive literature reviewStrong potential to lead to changes in therapeutic or preventive practices, which can be quickly integrated into the fieldApproach and methodsProduce results that are generalizable, multicentric projects must be favoredCo-recruitment should be encouraged when this does not compromise the validity and interpretation of the study, and on condition that it does not lead to over-solicitation of participantsConsiderations specific to the pandemic contextCollaboration must be encouraged, recognized and rewardedResearchers are invited to consult provincial, national and international registers of COVID-19 projects with a view to supporting open science

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https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-clinical-trials/list-authorized-trials.html

https://www.msss.gouv.qc.ca/professionnels/covid-19/outils-d-information-sur-la-covid-19/#pour-la-recherche-clinique

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Colcorona – a rct made in Quebec

Resolution trial – another rct made in Quebec

Conclusion

Perspectives

• Molecule: colchicine / centre: Montreal Heart Institute• Target: inflammatory storm • Primary objective of the COLCORONA study: to determine whether

short-term treatment with colchicine reduces the rate of death and lung complications related to COVID-19

• Target of enrollment: 6000 subjects diagnosed with COVID-19 but not hospitalized

• Availability of COLCORONA Clinical Trial: Montreal, New York City tri-state area of New York, New Jersey and Connecticut, California, Madrid-Spain, British Columbia, Ontario and more to come

• Molecule: LAU-7b – a novel and improved solid dosage form of fenretinide

• Company: Laurent Pharmaceuticals• Primary objective of the RESOLUTION study: to reduce the

severity of the disease and prevent its progression towards the Acute Respiratory Distress Syndrome (ARDS)

• The RESOLUTION trial follows the recommendations of WHO Master Protocol for COVID-19 clinical studies and will measure the patient health status on a 7-point ordinal scale as primary outcome.

• Target of enrollment: 200 hospitalized COVID-19 patients for a treatment duration of 14 days

• Phase II trial available in Montreal and more sites to come

• Unprecedented mobilization of researchers, MDs, pharmaceutical and biotech companies • Coordination effort in place to limit small, poorly designed, non-standardized assays, based on

insufficient assumptions• Participation in major international consortia: ACTIV; SOLIDARITY• The same usual suspects are found in Canadian studies but also promising innovations

5 KEY PRINCIPLES: importance, rigorous design, integrity, complete & prompt report, feasibility

Clinical research – health research – science have to remain high on the agendas to succeed in producing care and to carefully rethink and transform our health systems and approaches …

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VERY rapid review of SARS-CoV2 life cycle

Pr. Carlos Del RioCOVID-19 and Therapeutic Trials

Image by Feng He, et al

Open Forum Infectious Diseases, ofaa105, https://doi.org/10.1093/ofid/ofaa105

Treatment : Some Suggested Options

• Remdesivir• Chloroquine• Hydroxychloroquine• Lopinavir/ritonavir• Darunavir/cobicistat• Ribavirin• Nitazoxanide• Niclosamide• Favipiravir• Convalescent serum• Monoclonal antibody

• Nelfinavir• Penciclovir• Mefloquine• Oseltamivir• Immunomodulators

» Corticosteroids » Tocilizumab » INF-alpha (inhalational) » IVIG » Baricitinib » Interferon lambda

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What is Remdesivir?

Remdesivir record

Remdesivir safety

• Experimental antiviral drug• Possible mechanisms of action

» Directly interfere with RNA polymerase » It generates a nucleoside (adenosine) analogue that serves as substrate for RNA polymerase » RNA chain termination (similar concept than NRTI for HIV)

• High genetic barrier to resistance• Poor PO absorption » only available IV (and new studies coming on inhaled remdesivir!)

• Developed in 2009 by Gilead for Hep C treatment » didn’t work• Re-purposed in 2015 for Ebola: inhibited viral replication in rhesus macaques. RCT in 2018 in

DRC comparing remdesivir with Zmapp and other 2 monoclonal Ab » lower mortality with 2 monoclonal Ab compared to remdesivir and Zmapp

• Inhibits viral replication in cell cultures: SARS CoV, MERS-CoV, SARS CoV2 » human trials for COVID-19

• Nausea and Transaminitis (common, mild) » Mild, transient ALT or AST elevations were observed in 3 patients without abnormalities in total bilirubin, alkaline phosphatase, or albumin

» Of note COVID-19 is associated with transaminitis• Renal toxicity (theoretical, clinical relevance uncertain)

» Remdesivir coformulated with sulfobutylether beta cyclodextrin (SBECD) – theoretical nephrotoxicity risk in underlying renal dysfunction

» Renal dysfunction (CrCl < 50 or < 30) exclusion criteria for clinical trials• Hypotension (unclear)

» Among 175 patients receiving RDV in Ebola trial, 1 case of hypotension in a 41 year old prompting slowing of infusion, resulting in cardiac arrest and death

Kujawski SA, Wong KK, Collins JP, et al. medRxiv. March 2020:2020.03.09.20032896. doi:10.1101/2020.03.09.20032896Mulangu S, Dodd LE, Davey RT, et al. New England Journal of Medicine. 2019;381(24):2293-2303. doi:10.1056/NEJMoa1910993

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Remdesivir Clinical Trials

ACTT1

« TIME TO RECOVERY »

Seven ongoing registered clinical trials world-wide • Gilead Moderate COVID-19 (NCT04292730) (SIMPLE)

» Phase 3, Open label, Randomized. Enrollment = 1600 » 3 arms: (1) RDV 5 days, (2) RDV 10 days, (3) Standard of Care

• Gilead Severe COVID-19 (NCT04292899) (SIMPLE) » Phase 3, Open label, Randomized. E = 1600 » 2 arms: (1) RDV 5 days, (2) RDV 10 days

• NIAID Adaptive Trial (NCT04280705) (ACTT) » Phase 2, Blinded, Randomized. Enrollment = 800 » 2 arms: (1) RDV 10 days, (2) Placebo (adaptive)

• NIAID Combination Trial (NCT04401579) (ACTT-II) » Phase 2, Blinded, Randomized. Estimated enrollment = 1032 » 2 arms: (1) RDV 10 days + Baricitinib, (2) RDV 10 days + placebo (adaptive

• Double-blind, placebo controlled, randomized controlled trial• IV remdesivir vs. placebo• 200 mg IV loading dose X 1, followed by 100 mg IV daily• Up to 10 daily infusions• Assessments from day 1 to day 29• Main inclusion criteria: signs of pneumonia or SatO2 <94% or requiring supplemental O2• Main exclusion criteria: GFR < 30, ALT/AST > 5X ULN• Main outcome: TIME TO RECOVERY » stratified by disease severity• 1063 participants randomized: Feb 19 to April 21 2020

Definition: time when a participant satisfies categories 1, 2, or 3, on the following ordinal scale:1. Not hospitalized, no limitation of activities, not on O22. Not hospitalized, but limitation in activities or on O23. Hospitalized, not on O2, only for infection control purposes4. Hospitalized, not on O2, but requiring ongoing medical care5. Hospitalized, on O26. Hospitalized on NIPPV or HF O27. Hospitalized, on mechanical ventilation or ECMO8. Death

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Preliminary results (after DSMB analysis)

Definition: time when a participant satisfies categories 1, 2, or 3, on the following ordinal scale:1. Not hospitalized, no limitation of activities, not on O22. Not hospitalized, but limitation in activities or on O23. Hospitalized, not on O2, only for infection control purposes4. Hospitalized, not on O2, but requiring ongoing medical care5. Hospitalized, on O26. Hospitalized on NIPPV or HF O27. Hospitalized, on mechanical ventilation or ECMO8. Death

No difference in adverse events between groups either

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Preliminary results

Results of the results...

Remdesivir seems to work better if given earlier, before the onset of ARDS

• DSMB recommended participants unblinding if there were odds of benefiting from remdesivir »• ACTT2: initially four arm trial » now only two-arm trial• FDA: Emergency Use Authorization

• Feb 4, 2020 DHHS Secretary declared a public health emergency due to COVID-19• March 27 – Emergency Use Authorization (EUA) of drugs and biologics authorized• Three meds have been granted EUA

» Two FDA approved (chloroquine phosphate and hydroxychloroquine sulfate) » Remdesivir

• Only access of remdesivir through clinical studies, expanded access programs and compassionate use programs

• EUA issuance on May 1 to expand access to remdesivir

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Emergency Une Authorization (EUA)

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19The New England Journal of Medicine

• Recent example – peramivir in 2009-10 for H1N1 influenza, distributed by CDC

• Gilead announced donation of 1.5 million doses of remdesivir to the government

» Distribution by AmeriSourceBergen which has no control of which hospitals get drug

» «HHS distribution of remdesivir seems akin to winning the lottery — a random stroke of luck rather than a medically-informed decision,» Reps. Lloyd Doggett, D-Texas, and Rosa DeLauro, D-Conn., wrote in a May 13 letter to Health and Human Services Secretary Alex Azar.

https://www.npr.org/sections/health-shots/2020/05/14/855663819/remdesivir-distribution-causes-confusion-leaves-some-hospitals-empty-handed

This article was published on May 27, 2020, at NEJM.org

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Chloroquine and Hydroxychloroquine

• Common use for various rheumatologic conditions and malaria• Increases endosomal pH required for virus/cell fusion and interferes with the glycosylation of

cellular receptors of SARS-CoV-2• Immunomodulating activity

A total of 1542 patients were randomised to hydroxycholoroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25,7% hydroxychloroquine vs. 23,5% usual care; hazard ratio 1,11 [95% confidence interval 0,98-1,26]; p=0,10). Therer was also no evidence of beneficial effects on hospital stau duration or other outcomes.

Touret F, de Lamballerie X. Antiviral Research. 2020;177:104762. doi:10.1016/j.antiviral.2020.104762Yao X, Ye F, Zhang M, et al. Clin Infect Dis. doi:10.1093/cid/ciaa237

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

The New England Journal of Medicine

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CQ and HCQ Safety

Lopinavir/Ritonavir Vs. SOC in Severe Infection

• General (GI upset/nausea, dizziness) (common, mild)• Cardiotoxicity (long term use, rarely short term use)

» Conduction disorders most common, median treatment duration was 7 years but minimum duration was 3 days

• QTc prolongation (monitor) » One reported case of TdP (associated with long term HCQ use for SLE)

• G6PD Deficiency (unlikely clinical relevance)• Others (rare, long term use only)

» Retinopathy, Hematologic toxicities

Chin J Tuberc Respir Dis. 2020;43(0):E019. doi:10.3760/cma.j.issn.1001-0939.2020.0019Chatre C, Roubille F, Vernhet H, Jorgensen C, Pers Y-M. Drug Saf. 2018;41(10):919-931. doi:10.1007/s40264-018-0689-4Chen C-Y, Wang F-L, Lin C-C. Clin Toxicol. 2006;44(2):173-175. doi:10.1080/15563650500514558Mohammad S, Clowse MEB, Eudy AM, CriscioneSchreiber LG. Arthritis Care Res. 2018;70(3):481-485. doi:10.1002/acr.23296

N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282. [Epub ahead of print]

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US treatment Guidelines

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EIDD-2801

Summary of COVID-19 Treatments

• Orally available broad-spectrum antiviral ribonucleoside analog.• Effective in cell lines and primary human airway epithelial cultures against multiple coronaviruses

including SARS-CoV-2. • Drug developed by DRIVE, a non-for-profit biotechnology company owned by Emory University. • Licensed by Ridgeback • Phase 1 (NCT04392219) has begun.• Merck & Co announced plans to acquire Ridgeback to develop and commercialize it.

• Remdesivir is the only agent currently recommended for treatment of COVID-19, for use in patients with severe disease.

• Many trials of other agents are underway, but data do not support the use of other agents for treatment of COVID-19 at this time.

• There are no currently recommended preventive treatment options for COVID-19, although there are ongoing trials evaluating pre- and post-exposure interventions.

• No medications are currently US FDA approved for treatment of COVID-19.• Several medications that have US FDA approval for non-COVID-19 conditions are being

prescribed by clinicians for off-label use for COVID-19. » Antiviral agents (lopinavir/ritonavir) » Drugs originally approved as antimalarial agents (chloroquine and hydroxychloroquine) » immunomodulatory agents (IL-6 inhibitors: tocilizumab, sarilumab, and siltuximab).

• Convalescent plasma is also being tested in persons with COVID-19. • Clinical trials are ongoing with more than 500 interventional studies listed on Clinicaltrials.gov

as “recruiting”.

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Pr. Stanley PlotkinVaccine candidates against SARS-CoV-2

COVID-19 AND VACCINE TRIALS Chairmen : Patrick Netter, Arnold Migus, FRANCE

SARS-2 Coronavirus

Zhang et al, Vaccines 2020

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Viral Dynamics of SARS-CoV-2 in Infected Patients

Pan et al, Lancet 2020

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Infection fatality ratio

Shi et al, Lancet 2020

Verity et al, Lancet 2020

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Wrapp et al Science 2020

Padron-Regalado, E., Infect Dis Ther 2020

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Callaway E, Nature April 2020

N Lurie et al. N Engl J Med 2020;382:1969-1973.

Vaccine Platforms

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Pr. Adrian HillA Chimpanzee Adenoviral Vectored Vaccine against COVID-19

ChAdOx1 nCoV-19: The technologyReplication-deficient simian adenoviral vectored vaccine expressing nCoV-19 Spike

ChAdOx1 nCoV-19: The technologyReplication-deficient simian adenoviral vectored vaccine expressing nCoV-19 Spike

• Non-enveloped dsDNA virus, 90nm• Non-replicating due to E1 (and E3) gene deletion

» HEK293 or PERC6 cells supply E1 in trans• Using a simian adenovirus avoids issues with pre-

existing immunity to human adenoviruses• Antigen-encoding transgene under strong

constitutive mammalian promoter » Antigen is not a structural part of the virion vaccines using a single Ad serotype are structurally the same, regardless of Ag

» Antigen is expressed at high level after vaccination, inducing strong B and T cell responses

• Manufactured on a HEK293 cell line• 12 phase I studies, 330 subjects vaccinated

» Consistent safety profile and string immunogenicity after one dose

• Single dose• Safety record

> 6500 people• Fairly rapid manufacturing – being optimised for personalised cancer use• Originally developed for CD8+ T cell induction

» But good single dose antibody induction• Can be scaled up for large supply• Minimal anti-vector immunity

» Boosting possible• Lots of ChAd vectors available

» ChAdOx1, ChAdOx2, ChAd63, ChAd3, PanAd3 (from Vaccitech, GSK, Merck, Pfizer etc others)

» Also human adenovirus vectors Ad5 (CanSino) and Ad26 (Janssen)

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ChAdOx1 nCoV-19, pre-clinical immunogenicity

Mouse, T cells Mouse, Antibody

NHP, Antibody

Fig. 1. Summed splenic IFN- ELISpot responses of BALB/c (left panel) and CD-1 (right panel) mice, in response to peptides spanning the spike protein from SARS-CoV-2, nine or ten days post vaccination, with 1.7 × 1010 vp ChAdOx1 nCoV-19 or 8 × 109 vp ChAdOx1 GFP. Mean with SEM are depicted

Box and whisker plot of ELISA analysis of BALB/C mouse sera (Top panel) or CD-1 mouse sera (Bottom panel) incubated with purified protein spanning the S1 domain (left) or purified protein spanning the S2 domain (right) of the SARS-CoV-2 spike nine or ten days post vaccination, with ChAdOx1 nCoV-19 or ChAdOx1 GFP.

Mouse neutralising Abs also positive- not shown

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Vaccine efficacy in macaque monkeys

ChAdOx1 nCoV-19: preclinical efficacy and safety

ChAdOx1 nCoV-19: Clinical trials in the UK

• 6 vaccinated macaques, 3 controls• Single dose vaccination with ChAdOx1 nCoV-19• Stringent high dose SARS-CoV-2 challenge

• Striking reduction in lung viral loads, both lobes and BAL

• Pneumonia in 0/6 vaccinees but 2/3 controls• No nasal viral load difference• Better clinical findings

• No immunopathology post challenge

• Challenge studies nearing completion » Two studies in NHPs, prime only and prime boost, challenge

High efficacy in the first (RML) study » Two studies in ferrets, prime only and prime boost, challenge

• Assessed immunogenicity including Th1/Th2 response, efficacy (clinical scores and virus shedding), pathology after immunisation and challenge

• Data from the first NHP study reviewed by the Data Safety Monitoring Board before initiating clinical trials in late April

» Good safety, high efficacy against pneumonia

• Phase I/IIb (April – early May 2020) » Healthy adults 18-55 years » 1100 subjects single dose in RCT (1:1 randomisation), follow for safety, immunogenicity (ELISA, ELISpot, neut Abs) and efficacy

» 10 subjects 2 doses 4 weeks apart

AgeChAdOx1-nCoV19 Placebo

Single dose(n=2610)

Two dose(n=80)

Single dose(n=2610)

Two dose(n=80)

5 - 12 30 - 30 -56 - 70 30 30 10 10

70+ 50 50 10 10≥ 18 (main efficacy

study) 5000 - 5000 -

• Phase II/III (late May - June 2020) » Blinded RCT » Main efficacy study - 5000 adults

18 centres now » Primary efficacy endpoint:

PCR positive symptomatic cases » Paediatric and older age groups

(safety and immunogenicity)

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Where best to measure vaccine efficacy?

UK• Incidence declining

Brazil• High and increasing incidence

USA• Variable incidence – but lockdown being lifted

Other countries

ChAdOx1 nCoV-19: Manufacturing

Other vaccines: competitors or allies?

Undertaken in suspension HEK293 cells (tet-repressed) in disposable bioreactor bags

First GMP batch made in Oxford in March 2020

During March process tech transferred to Advent, Italy, for GMP batch of ~6000 doses: May 2020

Large scale manufacture now underway at risk in seven countries: in Europe, USA, Asia Yield at large scale = about 5 doses per ml Tech transfer to 2000L scale underway

Partnership with AstraZeneca has accelerated further clinical development and large scale low cost manufacture

• contracts announced with UK, US, Europe, India, LMICs• total dose target is now 2 billion doses over 12 months• 1 billion doses from Serum Institute of India contract alone

• Viral vectored vaccines » Ad5 (CanSino) – joint first to the clinic in mid-March 2020, phase III soon in Canada » ChAdOx1 nCoV-19 – phase I 23 April, phase III started May 2020 » Ad26 (Janssen) - ? July

• RNA / DNA vaccines » Moderna – joint first in clinic in mid-March » Biontech/ Pfizer – late April » Inovio – April, DNA with an electroporation device » Imperial College London - June » Curevac - ? June

• Protein in adjuvant vaccines » Novavax - June » GSK / Sanofi - ?late 2020

• Inactivated virus vaccines in adjuvant » Sinovac – April, phase III planned in Brazil » Sinopharm - April

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Pr. Gerd SutterMVA-SARS-2-S DZIF COVID-19 vaccine candidate for risk groups

Introduction to DZIF : translational infection R&D

DZIF TTU Emerging Infections

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Introduction to IDT

MVA-MERS-S blueprint

• Based on validated recombinant Modified vaccina virus Ankara vector platform, MVA-SARS-2-S was designed to follow the MVA-MERS-S development (Song F et al., 2013; Volz A et al., 2015)

• MVA-MERS-S has undergone phase I clinical testing at UKE and was selected by for phase Ib/IIa, II clinical development and vaccine stockpiling

» Phase I data show favourable safety and immunogenicity profile (Koch T et al., 2020)

» Start of phase Ib at UKE and EMC Rotterdam scheduled for 4Q20

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MVA-MERS-S phase I results

MVA-MERS-S phase I results ; cont’d

• H o m o l o g o u s p r i m e - a n d - b o o s t immunizations with MVA-MERS-S revealed a benign safety profile with only transient mild-to-moderate reactogenicity

• Participants experienced no severe or serious adverse events (AE)

• Local reactions (e.g. swelling, erythema, pain), headache and fatigue were the most common AE and seen in 69% (18/26), 62% (16/26) and 65% (17/26), respectively

• All AE resolved swiftly (median within one day) and without sequelae

• Following booster immunization, 87% (20/23) of all vaccinees showed seroconversion using an MERS-CoV-S1-ELISA

• Antibody titers correlated with MERS-CoV-specific neutralizing antibodies

• T-cell responses were detected in 87% of all vaccines

• RBD rich source of T cell epitopes

• T-cell responses were measured by IFN- ELISpot

• PBMCs were stimulated using five peptide pools (A)

• Median values of SFC/1M PBMCs (B)• Sum of medians of SFC per cohort, per

time point (C)

Lancet ID, Koch et al., April 2020

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MVA-SARS-2-S : design and preclinical

• MVA platform technology based on MVA F6 LMU

• Expression of full-length SARS-CoV-2 S gene sequence

• Production of mature ~190 kDa spike glycoprotein

• Genetic homogeneity, genetic identity, genetic stability

• Full growth capacity in avian cell substrates for manufacturing

• Non-replicating in human cell lines – BSL-1

Preclinical testing in miceSARS-CoV-2 neutralizing antibodiesSARS-CoV-2 specific CD8+ T cells

Preclinical testing in ferretsOngoing studies

MVA-SARS-2-S : clinical planning and outlook

• Paul-Ehrlich-Institut grants accelerated path to clinical testing for MVA-SARS-2-S, based on bridging aspects of preclinical dvpt

• With joint funding from DZIF and BMBF, manufacturing of MVA-SARS-2-S clinical trial material (CTM) and start of phase I clinical trial at UKE scheduled for 3Q2020

• Planning of phase I-III clinical testing within DZIF clinical trial centers in progress, funding request directed to BMBF

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Dr. Marco CavaleriHow to accelerate vaccine development by protecting volunteers and future vaccines

How Long Will a Vaccine Really Take?TYPICAL SCENARIO – FROM RESEARCH TO DISTRIBUTION

DESIRABLE SCENARIO – FROM RESEARCH TO DISTRIBUTION

https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html

https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html

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Preclinical data required to support proceeding to First-into-human clinical trials

Addressing the theoretical risk for SARS-CoV-2 vaccine-induced disease enhancement

• The extent of preclinical data required depends on the vaccine construct, the supportive data available for the construct and data from closely related products.

• If a platform technology utilized to manufacture a licensed vaccine or other investigational vaccines is well characterized, it is possible to use data from repeat dose toxicity studies, biodistribution studies from other products using the same platform

• vaccine product characterization and manufacturing should be adequate.• For all SARS-CoV-2 vaccine candidates it is necessary to obtain data in animals and to

characterize the immune response induced the vaccine, but no absolute need for data in animal challenge models

• preclinical models with MERS and SARS vaccines candidates pointed to risk of enhancement of disease (ED) and immunopathology.

• Risk unknown with SARS-COV2 but cannot be ignored• Few studies in animal models conducted to date evaluating the potential for SARS-COV-2

vaccine-induced ED. No clear outcome for ED so far. • limited availability of non-human primates could significantly delay clinical vaccine

development. • The need to address the potential for vaccine-induced enhanced disease should be based

on the totality of available data relevant to the particular vaccine immune response, e.g. Th1-type skewed immune responses, titres of neutralizing antibodies

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Clinical trials

Vaccines – +120 candidates in the pipeline

• Early clinical trials are recruiting adults including elderly, e.g. up to 70-75 years olds, in parallel of in rapid sequence - need for adequate justification and appropriate monitoring

• before Phase IIb/III studies, safety data from early phase trials need to be favorable and preliminary relevant immunogenicity data need to support the dose and schedule selected

• Prevention against symptomatic COVID 19 disease of any severity is an acceptable primary endpoint – other secondary endpoints related to prevention of severe disease and infection

• No need to be powered for subgroups such as age, but inclusion of elderly encouraged if posology adequate. Primary analysis should be in the seronegative at baseline.

• EMA open to discuss role of human challenge studies if deemed ethically acceptable

10 vaccines have already started Phase I or II studies

Plans to start gathering efficacy data since the summer for most advanced vaccines –others later in the year

Efficacy from field efficacy trials is expected in order to support licensing if the epidemiological situation still allow

Safety is crucial- fairly rapid vaccination might occur in millions or billions of people: we need to have minimal sufficient evidence at time of approval and close monitoring post-approval

Option for early approval such as Conditional marketing authorisation could be considered if preliminary evidence supports a positive benefit-risk profile

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Summary of activities

33 vaccines identified for interaction with EMA• Rapid scientific advice proceeding for advanced vaccines and

therapeutics• Discussion at EMA COVID Task Force on several aspects including

paediatric plans• Intense international collaboration: ICMRA, WHO, FDA, US ACTIV,

ACT• Support to EC initiatives on vaccines clinical trials and supply

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Pr. Jean-François DelfraissyExpertise and decision support in health crises

FRENCH SCIENTIFIC COUNCIL COVID-19 Chairmen : Patrick Netter, Arnold Migus, FRANCE

• End of December 2019 : The Pasteur Institute receives introductory information on a new emergent virus in China. A few days later, the WHO is alerting the world of a new coronavirus strain.

• 24th January 2020 : The 3 first COVID-19 cases are diagnosed on the French territory. First sequencing of the virus in the Pasteur Institute.

• 14th February 2020 : First death due to a SARS-CoV-2 infection in France. National strategy : limit the clusters, RT-PCR diagnosis limited, cluster and people with symptoms

• 6th March 2020 : Meeting of scientists group at the Elysée Palace• 10th March 2020 : Creation of the Scientific Council COVID-19• 12th March 2020 : Meeting with the President of the Republic• 15th March 2020 : The 100 deaths mark is crossed in France. National decision to close non

essential shops.• 17th March 2020 : The general lockdown starts at 12am. This measure will end on the 11th May

2020.• 23rd March 2020 : The law on emergency sanitary state comes comes into force. The Scientific

council finds its legal foundation in law as the “committee of scientists”.

COVID-19 pandemic history in France - First period

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Evolution of several indicators through the pandemic

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• Four first general strategy opinions » 12th, 14th, 16th, 23th of March 2020 » Closure of non essential jobs, elections, lockdown.

• General strategy opinion 2nd April 2020 » Lockdown impacts and issues, criteria regarding requirement for ending of it » Alerts on some specific populations (old people, vulnerable, precarity)

• General strategy opinion 20th April 2020 » Progressive end of lockdown and measures to enforce : lockdown ending on 11th May 2020

• General strategy opinion 2th June 2020 » 4 scenarios for the post end of lockdown period, including prevention and protection plan » Scenario 1 : a pandemic under control Scenario 3 : a diffuse and silent restart » Scenario 2 : several clusters as a sign of a restart » Scenario 3 : a diffuse and silent restart » Scenario 4 : critical phase

• In preparation » Who should we test now ? Systematic testing ? » How can we get ready for a second wave ? » Vaccine and prevention : which population should be prioritized ?

• Specific opinions and notes » Two opinions on the specific issues related to overseas territory » One note on issues in care homes » One note on maintaining social ties in times of epidemic and lockdown » Two notes on children and school in the context of the decision to reopen schools » Electoral process, specifically the organisation of the local election 2nd tour

• Not fully involved in the therapeutic and research issues » The CARE : Analysis, Research and Expertise Committee. Chaired by the Nobel Prize Laureate, Françoise Barré-Sinoussi

» Provide ministers with insights or recommendations on mobilizing our research and innovation capabilities to fight the epidemic.

Major opinions of the Scientific CouncilPublic Health issues and preparedness - Production of indicators

Specifics issues and research

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Indicators comparaisons with our european neighbours

• Expertise of the Scientific council and decision by the executive : most of proposals accepted. The “third medical power” is a figment of the imagination of the press. No influence of the Council on material issues as accessibility of testing or masks.

• A good level of communication and sharing of information, especially with healthcare agencies such as Santé Publique France

• A strong willing from the Scientific council to be transparent : publication of opinions and notes, auditions by the Nation Assembly, the Senate, the economic, social and environmental Council (CESE), intervention in the press…

• A call for a citizen committee, carried by the Scientific Council, the National Healthcare Commission and the National commission on human rights (not accepted).

• A constant doctrine of personal citizen responsibility and choices. Nothing imposed and voluntary choices for each measure : schools, tests, isolation post-end of lockdown for positive patients or patients at high risks...

• Publications : Atlani-Duault, L., Chauvin F., et al. Ending France’s COVID-19 Lockdown: Scientific Council seeks to balance conflicting public health traditions, The Lancet (accepted) ; Bakhta K., Atlani-Duault L., Benamouzing D., et al., FRANCE : LE CONSEIL SCIENTIFIQUE COVID-19, ROLE ET FONCTIONNEMENT, Revue médicale suisse (accepted).

Relation between scientists, politics and other realms

• Summer 2020 » The epidemic is so far under control » Scenarios and tools are ready to be activate now » More and more control indicators are being produced in order to monitor any sign of start to new epidemic

• Late 2020 » The Scientific council thinks that a second wave will probably happen, especially in the absence of stringent control measures. Why ?

Collective immunity is probably less than 10% Respiratory virus is in common circulation and because of seasonality SARS-CoV-2 is a coronavirus, but the pandemic is really similar to that of the flu. Data from the Southern hemisphere must be followed.

» Tools and control measures have to be enforceable at any time until the end of the year » Given the huge social and economic costs associated with a general lockdown, we have to design alternative control strategies that have the same impact on transmission but with reduced costs for society

What’s next ?

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Je tiens d’abord à vous remercier tous, orateurs, présidents et organisateurs de cette impressionnante réunion.Je dois vous rappeler qu’elle a lieu à l’occasion du bicentenaire de notre Académie française de médecine.Notre rencontre (comme l’ont rappelé ce matin Patrice Debré et notre président Jean-François Mattei) réunit à la fois actualité et histoire : la lutte contre Covid-19 est

liée et redevable à des siècles d’hygiène et de diverses mesures contre les maladies infectieuses depuis la découverte des microbes par Louis Pasteur comme agents causaux de maladies et les premières perspectives de vaccins.

L’ouverture de notre Ministre de la Santé et des Solidarités, Olivier VERAN, nous a rappelé l’importance de cette lutte qui fait désormais référence à la santé mondiale et aux vaccins comme un bien commun pour l’humanité.

Nous avons appris au cours des siècles passés que l’émergence des infections nécessitait de rassembler de multiples expertises, médecins et biologistes, vétérinaires, mais aussi écologistes, climatologues, ainsi que spécialistes des sciences humaines et sociales et spécialistes des technologies de la communication.À ce jour, nous ne pouvions pas gérer tous les aspects de cette nouvelle infection à Coronavirus. Nous avons dû faire des choix !D’autres réunions viendront, mais je tiens à souligner maintenant certains points principaux débattus aujourd’hui.Je veux évoquer en premier lieu, comme notre ministre de la Santé M. Olivier Véran l’a fait dans son introduction ce matin, aux travaux de notre Académie qui, ont émis plus de soixante déclarations, analyses et recommandations, seule ou avec des partenaires de la santé et des sciences Académies sœurs au cours des trois derniers mois et à travers de nombreux groupes de travail.

L’un des espoirs les plus attendus est de découvrir des traitements efficaces.Malheureusement, il n’existe à ce jour aucun traitement permettant de traiter spécifiquement la Covid-19 à différents stades de son développement, de sa prévention à ses complications les plus sévères.Aucun médicament n’est actif non plus contre les infections antérieures dues à d’autres coronavirus chez l’homme (comme le SRAS et le MERS).Les médicaments actuellement étudiés sont ce que l’on appelle des « médicaments repositionnés », des médicaments qui ont été conçus pour d’autres conditions. Ils peuvent avoir un effet in vitro sur la réplication du virus, sur son entrée ou sa sortie de la cellule, ou sur l’activation du système immunitaire.Mais aucun d’entre eux n’est cependant dépourvu d’effets secondaires et leur évaluation doit être basée sur le rapport bénéfice / risque.Aujourd’hui, nous avons également vu certains des essais menés dans le monde. Ils nous ont montré un effort national et collectif extraordinaire.Si nous réunissons toutes les données que nous avons des différentes tentatives internationales, que pouvons-nous conclure à ce moment, maintenant?

Alors que la pandémie a touché près de cinq millions de personnes en six mois et tué plus de trois cent mille personnes, aucun essai n’a encore identifié un traitement capable de réduire la mortalité Covid-19.

Mais le nombre d’essais n’est pas le facteur limitant : les plateformes ClinTrials Gov aux États-Unis, EudraCT

CONCLUSION DU SECRÉTAIRE PERPÉTUEL

Professor Jean François ALLILAIREPerpetual Secretary of the French Academy of MedicineSecrétaire perpétuel de l’Académie nationale de médecine

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dans l’Union européenne et ChiCTR en Chine, ont identifié plus de quinze cents études.Outre le petit nombre de médicaments testés, les réserves méthodologiques et les biais sont multiples :

• Premièrement : l’absence fréquente d’un groupe témoin adapté au médicament supposé actif, ou l’absence de randomisation.

• Ensuite : seuls quelques essais comparent le traitement testé avec un placebo en double aveugle.• Ensuite : près de la moitié des essais rapportés dans ClinTrials Gov seraient « compatissants ».• Sans groupe témoin, ils ne seront guère utilisables car l’histoire naturelle des maladies Covid-19 est

variable sans être précisément connue : ils répondent bien à l’empathie des médecins mais mal à la recherche clinique.

Ils peuvent même freiner cette dernière en réduisant le nombre de patients qui accepteraient, dans notre contexte d’incertitude, de bénéficier des soins mieux standardisés dispensés dans le cadre de la recherche.

Une deuxième difficulté est l’hétérogénéité des patients :Il concerne l’âge, le sexe, les comorbidités antérieures et l’expression de leur maladie au moment de l’inclusion (je veux dire la présence ou l’absence d’hypoxie, d’inflammation, de coagulopathie).

La troisième difficulté concerne le principal critère de jugement. Un critère décisif chez les patients hospitalisés atteints d’une maladie grave est la mortalité de toutes causes.La mort est le résultat d’une minorité de cas symptomatiques, même dans les formes sévères ; cela implique des essais de très grande envergure ou la méta-analyse d’essais concordants dans leurs critères d’inclusion et de jugement, mais l’hétérogénéité de ces critères empêchera les méta-analyses ultérieures.

Enfin, les grands essais coopératifs sont très redondants.

Le contexte d’urgence semble avoir motivé la tolérance pour les essais sans expertise méthodologique suffisante et dispersé l’effort de recherche clinique.Cette dispersion reflète également l’autorité insuffisante de l’OMS (Organisation mondiale de la santé) et le manque d’action concerté entre les agences nationales du médicament, même au sein de l’Union européenne.Ce manque de coordination et de coopération dans les essais thérapeutiques au niveau national, européen et international est donc très regrettable.Dans une pandémie comme dans une situation ordinaire, répétons que les règles d’évaluation critique des méthodes et des résultats doivent s’appliquer. Il en est de même de l’éthique scientifique et médicale, du respect de l’intégrité scientifique et de l’éthique de la communication des résultats.Des considérations similaires s’appliquent au vaccin, qui est désormais le principal espoir dans la lutte contre la Covid-19. Nous avons vu aujourd’hui un certain nombre d’efforts et d’espoirs de vaccination dans le monde.Ils perdurent mais un certain nombre de goulots d’étranglement doivent être signalés et doivent être corrigés par des initiatives à encourager.

* Des efforts de recherche sont encore nécessaires pour mieux comprendre les corrélats de la protection de l’immunité naturelle et guider le processus de vaccination nécessaire pour prévenir l’infection et / ou la maladie.L’établissement et l’étude de modèles animaux, ainsi qu’une meilleure compréhension du rôle joué par l’immunité innée et adaptative, qu’elle soit humorale ou cellulaire, devraient légitimement y contribuer.* Les différentes phases des essais cliniques, de la tolérance à l’efficacité, sont longues et coûteuses compte tenu du nombre de vaccins candidats à tester, cela nécessitera des stratégies et des protocoles coordonnés appropriés.* Le niveau d’exigence des autorités réglementaires diffère beaucoup entre elles, en particulier FDA, EMA etc... Les prérequis doivent être établis en coordination suffisamment tôt. Les différentes étapes de l’enregistrement doivent être accompagnées pour permettre un délai de commercialisation rapide.* Les vaccins devront être produits en quantité suffisante et pouvoir être mis à la disposition de toutes les populations. La capacité de production doit être préalablement évaluée et adaptée aux besoins.Les chaînes de distribution doivent être assurées pour une livraison appropriée.* Des informations sur les performances des vaccins et leurs différentes étapes de production doivent être

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régulièrement fournies aux parties prenantes.L’éducation du public doit être assurée pour garantir l’utilisation rationnelle et efficace du vaccin afin d’assurer une protection individuelle mais aussi collective afin de bloquer la propagation du virus et sa résurgence.Toutes ces considérations sur les traitements et les vaccins nous incitent à promouvoir la recherche sur la physiopathologie de la maladie.Nous avons vu aujourd’hui à quel point l’interaction de l’hôte et du virus est subtile. Elle est et doit rester la base des réflexions futures sur tous les aspects thérapeutiques et préventifs de cette infection.Cela signifie que la recherche doit être fortement soutenue, qu’elle soit clinique, fondamentale et translationnelle.Il reste, enfin et surtout, que la confrontation de nos politiques publiques dans la lutte contre la Covid-19, requiert la plus grande attention.Les présentations du matin ont montré combien il est important de comparer nos expériences, mais aussi combien il est nécessaire de s’entendre à l’avance pour échanger et si possible coordonner nos efforts.Il apparaît que seule la gouvernance partagée, que nous souhaitons appeler, nous permettra d’aller plus loin ensemble et de renforcer ou créer les instruments de repérage et de traitement des urgences infectieuses.

Au terme de ma trop longue conclusion, en analyse de la journée, je veux dire quelques mots sur la mission et l’action de notre Académie française et ses perspectives.

Instituée en tant qu’organisme indépendant il y a deux siècles, l’Académie française de médecine a pour vocation d’offrir aux autorités de santé publique des informations et des déclarations scientifiques pour conduire les politiques publiques de recherche et de formation, mais aussi de participer au débat public sur la santé en France et à l’étranger.Tel est le souhait de ceux qui l’ont créé il y a deux cents ans. Mais si les épizooties sont toujours une lutte avec sa part de souffrances et de risques, l’environnement général et le contexte ont changé.Plus que jamais, la lutte est internationale et implique des collaborations renouvelées.Cela montre l’importance que nous devons attacher au développement de notre politique internationale, à ses partenariats, à ses missions et à ses modes d’action. Nous entendons donc continuer à diffuser et promouvoir les différentes modalités de l’expertise française (à travers le monde), multiplier nos efforts pour favoriser les collaborations et les échanges, conseiller nos ambassades et les aider dans les missions qu’elles ont pour favoriser les interactions partenaires, affirmer notre présence dans les organisations internationales, fédérer les forces motrices de la France pour accroître son efficacité à l’international et en Europe, renforcer les compétences des partenaires qui le souhaitent, notamment dans le monde francophone, et s’entraider pour toutes ces actions de nos membres étrangers.

Mesdames et messieurs, chers collègues,La médecine et la science sont les meilleurs vecteurs de solidarité et de développement humain. La Covid-19 nous rappelle plus que jamais que nous devons travailler ensemble pour le bien mondial de la santé publique. Les technologies d’aujourd’hui nous aident.

Une journée comme celle-ci montre que nos rencontres, bien que virtuelles, peuvent être très riches.De nouvelles perspectives s’ouvrent à nous, l’Académie nationale de France, à des institutions partenaires en France et à l’étranger, pour savoir conduire ces échanges d’informations scientifiques, l’éducation du public, promouvoir des réseaux d’échanges et suivre les efforts de lutte contre la Covid-19, mais pas seulement, dynamisez les collaborations.Que ce Webinaire soit à l’origine de nouveaux échanges, et se donne la perspective de les renouveler.

Merci tout le monde et j’espère à bientôt pour de nouvelles opportunités d’échanges.

1820 - 2020100

I want first thank you all, speakers, chairmen and organizers of this impressive meeting.I must remind you that it takes place in the bicentenary of our French Academy of medicine. Our meeting, (as Patrice Debré and our president Jean-François Mattei recalled this morning ) brings together both actuality and history : the fight against Covid-19 is linked and redevable with centuries of Hygiene and diverse measures against infectious diseases since the discovery of microbes by Louis Pasteur as causal agents of diseases, and the first vaccines prospects.

The opening of our Health and Solidarities Minister Olivier VERAN reminded us of the importance of this struggle, which refers now to global health and vaccines as a common good for humankind.

We’ve learned from past centuries that the emergence of infections required bringing together multiple expertises, doctors and biologists, veterinarians, but also ecologists, climate scientists,as well as human and social scientists, and specialists in communication technology. To day, we could not deal with all aspects of this new Coronavirus infection. We had to make choices! Other meetings will come, but I want emphasize now some main points discussed today. I want to refer first , as our minister of Heath Mr Olivier Véran did in his introduction this morning, to the works of our Academy which, have issued more than sixty statements, analyzes and recommendations on her own or with partner health and sciences Sister academies over the past three months and through many working groups.

One of the most awaited hopes is to discover efficient treatments.Unfortunately, there is no treatment until now to specifically treat Covid-19 at different stages of its development, from its prevention, to its most severe complications. No drugs are either active against previous infections due to other coronaviruses in humans (like SARS & MERS). The drugs currently studied are what is called « repositioned drugs » drugs that have been designed for other conditions. They can have an in vitro effect on the replication of the virus, on its entry or exit from the cell, or on the activation of the immune system. But none of them however is devoid of side-effects and their evaluation is to be based on benefit / risk ratio. Today we have also seen some of the trials being done around the world. They showed us an extraordinary national and collective efforts. If we join together all the data that we have of the various international attempts, what can we conclude at this time, now ?

While the pandemic has affected nearly five million people in six months and killed more than three hundred thousand people, no trial has yet identified a treatment that can reduce mortality Covid-19 mortality. But the number of trials is not the limiting factor: the ClinTrials Gov platforms in the USA, EudraCT in the European Union and ChiCTR in China, have identified more than fifteen hundred studies. In addition to the small number of drugs tested, the methodological reserves and bias are multiple:

• First : the frequent absence of a control group adapted to the supposedly active drug, or the lack of randomization.

• Then : only few trials compare the treatment tested with placebo in a double-blind fashion. • Then : almost half of the trials reported in ClinTrials Gov are said to be « compassionate ». • Without a control group, they will hardly be usable because the natural history of Covid-19 diseases is

variable without being precisely known: they respond well to physicians’ empathy but poorly to clinical research.

• They can even hinder the latter by reducing the number of patients who would accept, in our context of uncertainty, to benefit from the better standardized care given within the framework of research.

A second difficulty is the heterogeneity of the patients: It concerns age, sex, previous comorbidities , and the expression of their disease at the time of inclusion (I mean presence or absence of hypoxia, inflammation, coagulopathy).

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The third difficulty concerns the main judgment criterion. A decisive endpoint in hospital patients with severe disease is all-cause mortality. Death is the outcome for a minority of symptomatic cases, even in severe forms; this implies very large trials or the meta-analysis of concordant trials in their inclusion and judgment criteria , but the heterogeneity of these criteria will preclude subsequent meta-analyzes.

Last but not least, the large cooperative trials are very redundant.

The emergency context seems to have motivated tolerance for trials without sufficient methodological expertise and dispersed the clinical research effort. This dispersion also reflects the insufficient authority of WHO ( the World Health Organization) and the lack of concerted action between national drug agencies, even within the European Union. This lack of coordination, and cooperation in therapeutic trials at a national, European and international level is therefore very regrettable. In a pandemic as well as in an ordinary situation, let us repeat that the rules of critical appraisal of methods and results must apply. The same applies to scientific and medical ethics respect for scientific integrity and the ethics of reporting results.Similar considerations apply to the vaccine, which is now the main hopes in the fight against Covid-19 . We have seen today a number of vaccine efforts and hopes around the world today. They continue but a certain number of bottlenecks must be pointed out and need to be remedied by initiatives to be encouraged.*Research efforts are still necessary to better understand the correlates of protection of natural immunity and guide the immunization process necessary to prevent infection and/or disease. The establishment and study of animal models, as well as a better understanding of the role played by innate and adaptive immunity, whether humoral or cellular, should legitimately contribute to this.*The different phases of clinical trials, from tolerance to efficacy, are long and expensive in view of the number of vaccine candidates to be tested, this will need appropriate coordinated strategies and protocols designs .*The level of requirement of the regulatory authorities differ very much between them, in particular FDA, EMA etc... The prerequisites must be established in coordination early enough. The different stages of registration should be accompanied to allow rapid time to marketing . *Vaccines will have to be produced in sufficient quantity and be able to be made available to all populations. Production capacity must be assessed beforehand and adjusted to the needs . Distribution chains must be insured for appropriate delivery.*Informations on the performance of vaccines and their different stages of production must be regularly provided to stakeholders. Public education must be provided to guarantee the rational and effective use of the vaccine in order to ensure individual but also collective protection so as to block the spread of the virus and its resurgence.All these considerations on treatments and vaccines encourage us to promote the research on the pathophysiology of the disease. We have seen today how subtle the interaction of the host and the virus are. It is and must remain the basis of the future reflections on all the therapeutic and preventive aspects of this infection. This means that research must be strongly supported, whether clinical, fundamental and translational.It remains, last but not least, that the confrontation of our public policies in the fight against the Covid-19, requires the greatest attention. The presentations in the morning showed how important it is to compare our experiences, but also how necessary it is to agree in advance to exchange views, and if possible coordinate our efforts. It appears that only shared governance, which we want to call for, will allow us to go further together and strengthen or create the instruments for the stakeout and treatment of infectious emergencies.

At the end of my too long conclusion, in analysis of the day, I want to say some more words on the mission and action of our French Academy and its perspectives.

1820 - 2020102

Established as an independent body two centuries ago, the French Academy of Medicine aims to offer to public health authorities scientific information and statement to conduct public policies in research and training, but also participate to the public debate on health in France and elsewhere. This is the wish of those who created it two hundred years ago. But if epizootics are still a struggle with its share of suffering and risks, the general environment and context have changed. More than ever, the struggle is international and involves renewed collaborations. This shows the importance we must attach to the development of our international policy, to its partnerships, to its missions, and to its modes of action. We thus intend to continue to disseminate and promote the different modalities of French expertise (around the world), to multiply our efforts to promote collaborations and exchanges, advise our embassies and help them in the missions they have to foster partner interactions, assert our presence in international organizations, bring together the driving forces of France to increase its efficiency internationally and in Europe, strengthen the skills of partners who wish to do so, particularly in the French-speaking world, and help each other in this for all these actions of our foreign members.

Ladies and gentlemen, dear colleagues,Medicine and science are the best vehicle for solidarity and human development. Covid-19 reminds us more than ever that we need to work together for the global good of public health. Today’s technologies are helping us.

A day like this shows that our meetings, although virtual, can be very rich. New perspectives open to us, the National Academy of France, to partner institutions in France and elsewhere, to know how to conduct these exchanges of scientific information, public education, promote networks of exchanges and monitoring efforts to fight against the Covid-19, - but not only -, energize collaborations. May this Webinar be at the origin of new exchanges, and give itself the prospect of renewing them.

Thank you to every one and I hope to see you soon for new exchange opportunities.

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Académie nationale de médecine16 rue Bonaparte, 75006 Paris

Tél : 01 42 34 57 70www.academie-medecine.fr

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