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Because of the rapid worldwide propagation of COVID‐19 (coronavirus disease 2019), each health care system had to urgently adapt with all efforts aimed to maximize the capacity of treatment for infected patients. With this in mind, the President of the French Republic declared on March 12, 2020: “Non‐essential hospital care will be postponed, i.e. surgical procedures that are not urgent.” But, in spite of the effort deployed by each hospital to provide a sufficient capacity of treatment for patients requiring a surgical procedure as an emergency, we have observed that the management of these patients have been largely affected, not because of a lack of resources but because of a surprising lack of patients.

International audience; BackgroundPRIMVAC is a VAR2CSA-derived placental malaria vaccine candidate aiming to prevent serious clinical outcomes of Plasmodium falciparum infection during pregnancy. We assessed the safety and immunogenicity of PRIMVAC adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) in French and Burkinabe women who were not pregnant.MethodsThis first-in-human, randomised, double-blind, placebo-controlled, dose escalation trial was done in two staggered phases, a phase 1A trial in 18–35-year-old women who were malaria naive in a hospital in France and a subsequent phase 1B trial in women who were naturally exposed to P falciparum and nulligravid in the clinical site of a research centre in Burkina Faso. Volunteers were recruited into four sequential cohorts receiving PRIMVAC intramuscularly at day 0, 28, and 56: two cohorts in France receiving 20 μg or 50 μg of PRIMVAC and then two in Burkina Faso receiving 50 μg or 100 μg of PRIMVAC. Volunteers were randomly assigned (1:1) to two groups (PRIMVAC adjuvanted with either Alhydrogel or GLA-SE) in France and randomly assigned (2:2:1) to three groups (PRIMVAC adjuvanted with either Alhydrogel, GLA-SE, or placebo) in Burkina Faso. Randomisation was centralised, using stratification by cohort and blocks of variable size, and syringes were masked by opaque labels. The primary endpoint was the proportion of participants with any grade 3 or higher adverse reaction to vaccination up until day 35. Safety at later time points as well as humoral and cellular immunogenicity were assessed in secondary endpoints. This trial is registered with ClinicalTrials.gov, NCT02658253.FindingsBetween April 19, 2016, and July 13, 2017, 68 women (18 in France, 50 in Burkina Faso) of 101 assessed for eligibility were included. No serious adverse event related to the vaccine occurred. PRIMVAC antibody titres increased with each dose and seroconversion was observed in all women vaccinated with PRIMVAC (n=57). PRIMVAC antibody titres reached a peak (geometric mean 11 843·0, optical density [OD] 1·0, 95% CI 7559·8–18 552·9 with 100 μg dose and GLA-SE) 1 week after the third vaccination (day 63). Compared with Alhydrogel, GLA-SE tended to improve the PRIMVAC antibody response (geometric mean 2163·5, OD 1·0, 95% CI 1315·7–3557·7 with 100 μg dose and Alhydrogel at day 63). 1 year after the last vaccination, 20 (71%) of 28 women who were vaccinated with PRIMVAC/Alhydrogel and 26 (93%) of 28 women who were vaccinated with PRIMVAC/GLA-SE still had anti-PRIMVAC antibodies, although antibody magnitude was markedly lower (452·4, OD 1·0, 95% CI 321·8–636·1 with 100 μg dose and GLA-SE). These antibodies reacted with native homologous VAR2CSA expressed by NF54-CSA infected erythrocytes (fold change from baseline at day 63 with 100 μg dose and GLA-SE: 10·74, 95% CI 8·36–13·79). Limited cross-recognition, restricted to sera collected from women that received the 100 μg PRIMVAC dose, was observed against heterologous VAR2CSA variants expressed by FCR3-CSA (fold change from baseline at day 63: 1·49, 95% CI 1·19–1·88) and 7G8-CSA infected erythrocytes (1·2, 1·08–1·34).InterpretationPRIMVAC adjuvanted with Alhydrogel or GLA-SE had an acceptable safety profile, was immunogenic, and induced functional antibodies reacting with the homologous VAR2CSA variant expressed by NF54-CSA infected erythrocytes. Cross-reactivity against heterologous VAR2CSA variants was limited and only observed in the higher dose group. An alternate schedule of immunisation, antigen dose, and combinations with other VAR2CSA-based vaccines are envisaged to improve the cross-reactivity against heterologous VAR2CSA variants.FundingBundesministerium für Bildung und Forschung, through Kreditanstalt für Wiederaufbau, Germany; Inserm, and Institut National de Transfusion Sanguine, France; Irish Aid, Department of Foreign Affairs and Trade, Ireland.

Facing the arrival of the COVID-19 pandemic in France, Santé Publique France has set up an evolutionary surveillance system based on definitions of possible, probable and confirmed cases. But only cases confirmed by SARSCoV-2, RT-PCR (reverse transcriptase polymerase chain reaction) or serology, hospitalized cases and in-hospital deaths have been recorded on a daily basis. COVID-19 actual incidence has thus been estimated through additional indicators such as specific calls to emergency services (Samu) and SOS doctors, emergency rooms visits, or consultations in a sentinel network of general practitioners. Surveillance of non-hospital mortality has been impaired by delays and diagnostic inaccuracies of death certificates. Only in-hospital lethality could be reliably monitored.With a few essential statistical precautions and working hypotheses, models made it possible to anticipate the evolution of the epidemic based on two essential indicators: the reproduction ratio R, and the epidemic doubling time. In Ile-de-France region, the Greater Paris University Hospitals Group has used its data warehouse to complete this epidemic dashboard, including a fine modeling of patients’ care pathways. All these indicators have proved essential to plan the response to this unprecedented crisis., Face à la crise sanitaire provoquée par la pandémie de Covid-19 en France, Santé publique France a mis en place un système de surveillance évolutif fondé sur des définitions de cas possible, probable et confirmé. Le décompte quotidien se limite cependant aux cas confirmés par reverse transcriptase polymerase chain reaction ou sérologie SARS-CoV-2 (actuellement via la plateforme SI-DEP), aux cas hospitalisés (via le Système d’information pour le suivi des victimes d’attentats) et aux décès hospitaliers par Covid-19. Ce suivi de la circulation virale est forcément non exhaustif, et l’estimation de l’incidence est complétée par d’autres indicateurs comme les appels au 15, les recours à SOS Médecins, les passages dans les services d’accueil des urgences, les consultations de médecine de ville via le réseau Sentinelle. Le suivi de la mortalité non hospitalière s’est heurté aux délais de transmission des certificats de décès et au manque de diagnostic fiable. Seule la létalité hospitalière a pu être mesurée de manière fiable. Moyennant un certain nombre de précautions statistiques et d’hypothèses de travail, les modèles ont permis d’anticiper l’évolution de l’épidémie à partir de deux indicateurs essentiels : le ratio de reproduction R et le temps de doublement épidémique. En Île-de-France, l’Assistance publique– Hôpitaux de Paris a complété ce tableau de bord grâce à son entrepôt de données de santé et a ainsi pu modéliser de manière fine le parcours de soins des patients. L’ensemble de ces indicateurs a été essentiel pour assurer une planification de la réponse à la crise.