Evaluation of Strategies to Fight COVID-19: The French Paradigm

(1) Background: We collected COVID-19 mortality data and the age distribution of the deceased in France and other European countries, as well as specifically in the cities of Paris and Marseille, and compared them. (2) Methods: Data on mortality related to COVID-19 and the associated age distribution were collected from government institutions in various European countries. In France, data were obtained from INSEE and Santé Publique France. All-cause mortality was also examined in order to study potential excess mortality using EuroMOMO. The Marseille data came from the epidemiological surveillance system. (3) Results: France is one of the European countries most impacted by COVID-19. Its proportion of deaths in people under 60 years of age is higher (6.5%) than that of Italy (4.6%) or Spain (4.7%). Excess mortality (5% more deaths) was also observed. Ile-de-France and the Grand-Est are the two French regions with the highest mortality. The proportion of deaths in the under-60 age group was considerable in Ile-de-France (9.9% vs. 4.5% in the Southern region). There are significantly higher numbers of patients hospitalized, in intensive care and deceased in Paris than in Marseille. (4) Conclusions: No patient management, i.e., from screening to diagnosis, including biological assessment and clinical examination, likely explains the high mortality associated with COVID-19

Epidemiological surveillance based on clinical laboratory data : interest and ability of MALDI-TOF mass spectrometry

Tous les agents infectieux n’ont en effet pas le même potentiel épidémique, et celui-ci peut fortement varier au sein d’une même espèce. L’identification bactérienne de routine est maintenant le plus souvent réalisée par spectrométrie de masse MALDI-TOF, dont l'utilité en épidémiologie a été démontré dans de nombreuses études. L’objectif principal de la thèse est de compléter la surveillance épidémiologique bactérienne déjà en place par une filière de traitement des spectres MALDI-TOF et ainsi faciliter par ailleurs la pré-investigation épidémiologique in-silico. Une étude descriptive sur la variabilité des spectres au sein d’une même espèce a été menée en explorant les diversités d'expression des pics des spectres MALDI-TOF. Les résultats ont permis d’apporter des éléments de compréhension sur l’organisation latente des pics co-occurrents en distinguant des pics communs d’espèce et des pics secondaires soutenant la discrimination de sous-populations. Une nouvelle filière de traitement des spectres MALDI-TOF a ainsi pu être construite. Son objectif est de rechercher l'existence de clusters présentant une proximité protéique dans une même temporalité. Ce processus s'appuie sur plusieurs méthodes spécifiques visant à contraster et à regrouper les spectres, à présenter graphiquement les résultats pour une interprétation épidémiologique facile, et à déterminer les pics spectraux discriminants avec leur possible identification à l'aide de bases de données de référence telles que UniProt. La filière fournit ainsi des informations essentielles sur une situation potentiellement épidémique.All infectious agents do not have the same epidemic potential, and this can vary greatly within the same species, which complicates the implementation of public health strategies. Currently, routine bacterial identification is most often performed by MALDI-TOF mass spectrometry. Several studies have demonstrated the ability of this technique for epidemiological investigation. The main objective of the thesis is to supplement the bacterial epidemiological surveillance already in place by a MALDI-TOF spectra analysis pipeline and thus facilitate the in-silico epidemiological pre-investigation.We carried out a descriptive study on the variability of the spectra within the same species by exploring the diversity of MALDI-TOF spectra peak expressions. The results showed the latent organization of co-occurring peaks by distinguishing between species specific peaks and secondary peaks supporting the discrimination of subspecies. Following these elements, a new process for analyzing MALDI-TOF spectra was thus able to be built. Its objective is to seek the existence of clusters of spectra presenting a protein proximity and appeared at the same time. This process relies on several specific methods aimed at contrasting and grouping the spectra, graphically presenting the results for easy epidemiological interpretation, and searching for the discriminating spectral peaks with their possible identification using reference databases, such as UniProt. This process aims at providing essential information on a potentially epidemic situation by giving valuable information for epidemiological sensemaking

Evaluation of Strategies to Fight COVID-19: The French Paradigm

International audience(1) Background: We collected COVID-19 mortality data and the age distribution of the deceased in France and other European countries, as well as specifically in the cities of Paris and Marseille, and compared them. (2) Methods: Data on mortality related to COVID-19 and the associated age distribution were collected from government institutions in various European countries. In France, data were obtained from INSEE and Santé Publique France. All-cause mortality was also examined in order to study potential excess mortality using EuroMOMO. The Marseille data came from the epidemiological surveillance system. (3) Results: France is one of the European countries most impacted by COVID-19. Its proportion of deaths in people under 60 years of age is higher (6.5%) than that of Italy (4.6%) or Spain (4.7%). Excess mortality (5% more deaths) was also observed. Ile-de-France and the Grand-Est are the two French regions with the highest mortality. The proportion of deaths in the under-60 age group was considerable in Ile-de-France (9.9% vs. 4.5% in the Southern region). There are significantly higher numbers of patients hospitalized, in intensive care and deceased in Paris than in Marseille. (4) Conclusions: No patient management, i.e., from screening to diagnosis, including biological assessment and clinical examination, likely explains the high mortality associated with COVID-19

Insights Into Subspecies Discrimination Potentiality From Bacteria MALDI-TOF Mass Spectra by Using Data Mining and Diversity Studies

Bacterial identification at subspecies level is critical in clinical care and epidemiological investigations due to the different epidemic potentialities of a species. For this purpose, matrix-assisted laser desorption ionization - time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed in place of molecular genotyping, but with some result discrepancies. The aim of this work is to methodically mine the expression diversities of MALDI-TOF bacterial species spectra and their possible latent organization in order to evaluate their subspecies specific expression. Peak expression diversities of MALDI-TOF spectra coming from routine identifications have been analyzed using Hill numbers, rarefaction curves, and peak clustering. Some size effect critical thresholds were estimated using change point analyses. We included 167,528 spectra corresponding to 405 species. Species spectra diversities have a broad size-dependent variability, which may be influenced by the kind of sampling. Peak organization is characterized by the presence of a main cluster made of the most frequently co-occurring peaks and around 20 secondary clusters grouping less frequently co-occurring peaks. The 35 most represented species in our sample are distributed in two groups depending on the focusing of their protein synthesis activity on the main cluster or not. Our results may advocate some analogy with genomics studies of bacteria, with a main species-related cluster of co-occurring peaks and several secondary clusters, which may host peaks able to discriminate bacterial subgroups. This systematic study of the expression diversities of MALDI-TOF spectra shows that latent organization of co-occurring peaks supports subspecies discrimination and may explain why studies on MALDI-TOF-based typing exhibit some result divergences

Using MALDI-TOF spectra in epidemiological surveillance for the detection of bacterial subgroups with a possible epidemic potential

International audienceAbstract Background For the purpose of epidemiological surveillance, the Hospital University Institute Méditerranée infection has implemented since 2013 a system named MIDaS, based on the systematic collection of routine activity materials, including MALDI-TOF spectra, and results. The objective of this paper is to present the pipeline we use for processing MALDI-TOF spectra during epidemiological surveillance in order to disclose proteinic cues that may suggest the existence of epidemic processes in complement of incidence surveillance. It is illustrated by the analysis of an alarm observed for Streptococcus pneumoniae. Methods The MALDI-TOF spectra analysis process looks for the existence of clusters of spectra characterized by a double time and proteinic close proximity. This process relies on several specific methods aiming at contrasting and clustering the spectra, presenting graphically the results for an easy epidemiological interpretation, and for determining the discriminating spectra peaks with their possible identification using reference databases. Results The use of this pipeline in the case of an alarm issued for Streptococcus pneumoniae has made it possible to reveal a cluster of spectra with close proteinic and temporal distances, characterized by the presence of three discriminant peaks (5228.8, 5917.8, and 8974.3 m/z) and the absence of peak 4996.9 m/z. A further investigation on UniProt KB showed that peak 5228.8 is possibly an OxaA protein and that the absent peak may be a transposase. Conclusion This example shows this pipeline may support a quasi-real time identification and characterization of clusters that provide essential information on a potentially epidemic situation. It brings valuable information for epidemiological sensemaking and for deciding on the continuation of the epidemiological investigation, in particular the involving of additional costly resources to confirm or invalidate the alarm. Clinical trials registration NCT03626987

Reply to Lebeaux D, Revest M. No evidence of clinical benefits of early treatment of COVID-19 patients with hydroxychloroquine and azithromycin

International audienc

Does SARS-CoV-2 re-infection depend on virus variant?

International audienc

Consequences of the COVID-19 Outbreak Lockdown on Non-Viral Infectious Agents as Reported by a Laboratory-Based Surveillance System at the IHU Méditerranée Infection, Marseille, France

International audienceThe objective of this paper is to describe the surveillance system MIDaS and to show how this system has been used for evaluating the consequences of the French COVID-19 lockdown on the bacterial mix of AP-HM and the antibiotic resistance. MIDas is a kind of surveillance activity hub, allowing the automatic construction of surveillance control boards. We investigated the diversity and resistance of bacterial agents from respiratory, blood, and urine samples during the lockdown period (from week 12 to 35 of 2020), using the same period of years from 2017 to 2019 as control. Taking into account the drop in patient recruitment, several species have exhibited significant changes in their relative abundance (either increasing or decreasing) with changes up to 9%. The changes were more important for respiratory and urine samples than for blood samples. The relative abundance in respiratory samples for the whole studied period was higher during the lockdown. A significant increase in the percentage of wild phenotypes during the lockdown was observed for several species. The use of the MIDaS syndromic collection and surveillance system made it possible to efficiently detect, analyze, and follow changes of the microbiological population as during the lockdown period

SARS-CoV-2: fear versus data

International audienc

Temporal and age distributions of SARS-CoV-2 and other coronaviruses, southeastern France

Objectives: The SARS-CoV-2 epidemic presents a poorly understood epidemiological cycle. We aimed to compare the age and weekly distributions of the five human coronaviruses, including SARS-CoV-2, that circulated in southeastern France. Methods: We analyzed all available diagnoses of respiratory viruses, including SARS-CoV-2, performed between 09/2013 and 05/2020 at the University Hospital Institute Mediterranee Infection in Marseille, southeastern France. Results: For SARS-CoV-2, positive children <15 years of age represented 3.4% (228/6,735) of all positive cases, which is significantly less than for endemic coronaviruses (46.1%; 533/1,156; p < 0.001). Among 10,026 patients tested for SARS-CoV-2 and endemic coronaviruses in 2020, children <15 years represented a significantly lower proportion of all positive cases for SARS-CoV-2 than for endemic coronaviruses [2.2% (24/1,067) vs. 33.5% (149/445), respectively; p < 0.001]. Epidemic curves for endemic coronaviruses and SARS-CoV-2 in 91,722 patients showed comparable bell-shaped distributions with a slight time lag. In contrast, the age distribution of endemic coronaviruses and 14 other respiratory viruses differed significantly compared to that of SARS-CoV-2, which was the only virus to relatively spare children. Conclusions: We observed for SARS-CoV-2 a temporal distribution resembling that of endemic coronaviruses but an age distribution that relatively spares the youngest subjects, who are those the most exposed to endemic coronaviruses. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases