Publications by authors named "Philippe Colson"

305 Publications

The puzzling mutational landscape of the SARS-2-variant Omicron.

J Med Virol 2022 Jan 8. Epub 2022 Jan 8.

Department of Biology, Aix-Marseille Université, Marseille, France.

The recently emerging SARS-CoV-2 variant omicron displays an unusual association of 30 mutations, 3 deletions, and 1 insertion. To analyze the impact of this atypic mutational landscape, we constructed a complete structure of the omicron spike protein. Compared with the delta variant, the receptor-binding domain (RBD) of omicron has an increased electrostatic surface potential, but a decreased affinity for the ACE-2 receptor. The N-terminal domain (NTD) has both a decreased surface potential and a lower affinity for lipid rafts. The omicron variant is predicted to be less fusogenic and thus less pathogenic than delta, due to a geometric reorganization of the S1-S2 cleavage site. Overall, these virological parameters suggest that omicron does not have a significant infectivity advantage over the delta variant. However, in omicron, neutralizing epitopes are greatly affected, suggesting that current vaccines will probably confer little protection against this variant. In conclusion, the puzzling mutational pattern of the omicron variant combines contradictory properties which may either decrease (virological properties) or increase (immunological escape/facilitation) the transmission of this variant in the human population. This Janus-like phenotype may explain some conflicting reports on the initial assessment of omicron and provide new insights about the molecular mechanisms controlling its dissemination and pathogenesis worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.27577DOI Listing
January 2022

Heterogeneity in susceptibility to hydroxychloroquine of SARS-CoV-2 isolates.

Front Biosci (Landmark Ed) 2021 12;26(12):1493-1502

Institut Hospitalo-Universitaire Mediterranée Infection, 13005 Marseille, France.

Background: Despite the fact that the clinical efficacy of hydroxychloroquine is still controversial, it has been demonstrated in vitro to control SARS-CoV-2 multiplication on Vero E6 cells. In this study, we tested the possibility that some patients with prolonged virus excretion could be infected by less susceptible strains.

Method: Using a high-content screening method, we screened 30 different selected isolates of SARS-CoV-2 from different patients who received azithromycin ± hydroxychloroquine. We focused on patients with viral persistence, i.e., positive virus detection in a nasopharyngeal sample ≥10 days, and who were tested during two French epidemic waves, late winter-spring of 2020 and the summer of 2020. Dose-response curves in single-molecule assays with hydroxychloroquine were created for isolates with suspected reduced susceptibility. Genome clustering was performed for all isolates.

Results: Of 30 tested strains, three were detected as replicating in the presence of azithromycin + hydroxychloroquine, each at 5 μM. The dose-response model showed a decrease in susceptibility of these three strains to hydroxychloroquine. Whole genome sequencing revealed that these three strains are all from the second epidemic wave and two cluster with isolates from Africa.

Conclusions: Reduced susceptibility to hydroxychloroquine was not associated with viral persistence in naso-pharyngeal samples. Rather, it was associated with occurring during the second epidemic wave, which began in the summer and with strains clustering with those with a common genotype in Africa, where hydroxychloroquine was the most widely used.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.52586/5043DOI Listing
December 2021

Incidence and Outcome of Coinfections with SARS-CoV-2 and Rhinovirus.

Viruses 2021 12 16;13(12). Epub 2021 Dec 16.

Institut Hospitalo-Universitaire Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13385 Marseille, France.

Background: We aimed to compare the clinical severity in patients who were coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rhinovirus or monoinfected with a single one of these viruses.

Methods: The study period ranged from 1 March 2020 to 28 February 2021 (one year). SARS-CoV-2 and other respiratory viruses were identified by real-time reverse-transcription-PCR as part of the routine work at Marseille University hospitals. Bacterial and fungal infections were detected by standard methods. Clinical data were retrospectively collected from medical files. This study was approved by the ethical committee of our institute.

Results: A total of 6034/15,157 (40%) tested patients were positive for at least one respiratory virus. Ninety-three (4.3%) SARS-CoV-2-infected patients were coinfected with another respiratory virus, with rhinovirus being the most frequent (62/93, 67%). Patients coinfected with SARS-CoV-2 and rhinovirus were significantly more likely to report a cough than those with SARS-CoV-2 monoinfection (62% vs. 31%; = 0.0008). In addition, they were also significantly more likely to report dyspnea than patients with rhinovirus monoinfection (45% vs. 36%; = 0.02). They were also more likely to be transferred to an intensive care unit and to die than patients with rhinovirus monoinfection (16% vs. 5% and 7% vs. 2%, respectively) but these differences were not statistically significant.

Conclusions: A close surveillance and investigation of the co-incidence and interactions of SARS-CoV-2 and other respiratory viruses is needed. The possible higher risk of increased clinical severity in SARS-CoV-2-positive patients coinfected with rhinovirus warrants further large scale studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13122528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709236PMC
December 2021

Epidemiology and genomic characterisation of travel-associated and locally-acquired influenza, Marseille, France.

Travel Med Infect Dis 2021 Dec 15;45:102236. Epub 2021 Dec 15.

IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France. Electronic address:

Background: The purpose of the study was to challenge the hypothesis of an introduction of influenza viruses by international travellers and subsequent local circulation in Marseille, France.

Methods: We analysed the epidemiological data of PCR-confirmed cases over an eight-year period and compared the genomic data of local and imported influenza viruses during a six-month period.

Results: Between June 2013 and December 2020, 12,434 patients in the Assistance Publique-Hospitaux de Marseille were diagnosed with an influenza virus infection at the laboratory of the Institut Hospitalo-Universitaire Méditerranéee Infection of Marseille. Half of the patients were below the age of 20. Most of the imported cases were diagnosed outside of epidemic periods. Fourteen genomes of the influenza A virus, including six in international travellers returning from Europe or from the Arabian Peninsula and eight from patients who had not travelled were analysed. Sequences of influenza A/H1N1 virus genomes detected in subjects who had travelled to Saudi Arabia were in the same clade and differed from sequences detected later in a traveller returning from Italy, and in non-travellers who were infected in Marseille. This suggests that influenza viruses imported from Saudi Arabia did not subsequently circulate in Marseille.

Conclusion: Future studies with higher numbers of genomes are needed to confirm this result.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tmaid.2021.102236DOI Listing
December 2021

Influenza A imported from Comoros to France in the summer months of 2021.

J Travel Med 2021 Nov 20. Epub 2021 Nov 20.

IHU-Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jtm/taab181DOI Listing
November 2021

Occurrence of a substitution or deletion of SARS-CoV-2 spike amino acid 677 in various lineages in Marseille, France.

Virus Genes 2021 Nov 27. Epub 2021 Nov 27.

IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13005, Marseille, France.

Great concerns have been raised about SARS-CoV-2 variants over the past six months. At the end of 2020, an increasing incidence of spike substitutions Q677H/P was described in the USA, which involved six independent lineages. We searched for changes to this amino acid in the sequence database of SARS-CoV-2 genomes obtained at the IHU Méditerranée Infection (Marseille, France) from 3634 patients sampled between February 2020 and April 2021. In seven genomes (0.2%), we found a deletion of five amino acids at spike positions 675-679 (QTQTN) including Q677, and in 76 genomes (2.3%) we found a Q677H substitution. The 83 genomes were classified in ten different Pangolin lineages. Genomes with a spike Q677 deletion were obtained from respiratory samples collected in six cases between 28 March 2020 and 12 October 2020 and in one case on 1 February 2021. The Q677H substitution was found in genomes all obtained from respiratory samples collected from 19 January 2021 and were classified in seven different lineages. Most of these genomes (41 cases) were of UK variant. Two others were classified in the B.1.160 Pangolin lineage (Marseille-4 variant) which was first detected in July 2020 in our institute but was devoid of this substitution until 19 January 2021. Also, eight genomes were classified in the A.27/Marseille-501 lineage which was first detected in our institute in January 2021 and which either harboured or did not harbour the Q677H substitution. Thus, the spike Q677H substitution should be considered as another example of convergent evolution, as it is the case of spike substitutions L18F, E484K, L452R, and N501Y which also independently appeared in various lineages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11262-021-01877-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627157PMC
November 2021

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.

Viruses 2021 10 28;13(11). Epub 2021 Oct 28.

Méditerranée Infection, Institut Hospitalier Universitaire, 13005 Marseille, France.

Background: Since the beginning of the COVID-19 pandemic, several SARS-CoV-2 variants have sequentially emerged. In France, most cases were due to spike D641G-harbouring viruses that descended initially from the Wuhan strain, then by the variant of B.1.160 lineage we called Marseille-4 since the summer of 2020, which was followed by the Alpha and Beta variants in early 2021, then the Delta variant currently.

Methods: We determined the neutralising antibody (nAb) titres in sera from convalescent individuals previously infected by these four major local variants and from vaccine recipients to the original Wuhan strain and nine variants, including two recent circulating Delta isolates.

Results: The results show high inter-individual heterogeneity in nAbs, especially according to the variant tested. The major variations among nAbs are based on the genotype responsible for the infection. Patients previously infected with the beta and B.1.160 variants had the lowest nAb titres. We show that this heterogeneity is well explained by spike protein mutants modelling using in silico approaches. The highest titres were observed in individuals vaccinated with the Pfizer/BioNTech COVID-19 vaccine, even against the delta variant.

Conclusions: Immunity acquired naturally after infection is highly dependent on the infecting variant, and, unexpectedly, mRNA-based vaccine efficacy was shown to be often better than natural immunity in eliciting neutralising antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13112177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623169PMC
October 2021

Isolation of 4000 SARS-CoV-2 shows that contagiousness is associated with viral load, not vaccine or symptomatic status.

Emerg Microbes Infect 2021 Dec;10(1):2276-2278

Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), Assistance Publique - Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Marseille, France.

Culture inoculation of 6722 nasopharyngeal samples since February 2020 allowed isolation of 3637 SARS-CoV-2 and confirmed that isolation rate is correlated to viral load, regardless symptomatology or vaccination status. Moreover, the delta variant is associated with higher viral loads and therefore higher rates of viral isolation, explaining its greater contagiousness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/22221751.2021.2008776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648030PMC
December 2021

Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV.

Future Microbiol 2021 11 10;16:1341-1370. Epub 2021 Nov 10.

Aix-Marseille Université, Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, 13005, France.

Since the beginning of the COVID-19 pandemic, large screening studies and numerous studies have assessed the antiviral activity of various drugs on SARS-CoV-2. In the context of health emergency, drug repurposing represents the most relevant strategy because of the reduced time for approval by international medicines agencies, the low cost of development and the well-known toxicity profile of such drugs. Herein, we aim to review drugs with  antiviral activity against SARS-CoV-2, combined with molecular docking data and results from preliminary clinical studies. Finally, when considering all these previous findings, as well as the possibility of oral administration, 11 molecules consisting of nelfinavir, favipiravir, azithromycin, clofoctol, clofazimine, ivermectin, nitazoxanide, amodiaquine, heparin, chloroquine and hydroxychloroquine, show an interesting antiviral activity that could be exploited as possible drug candidates for COVID-19 treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/fmb-2021-0019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579950PMC
November 2021

Clinical outcomes in patients infected with different SARS-CoV-2 variants at one hospital during three phases of the COVID-19 epidemic in Marseille, France.

Infect Genet Evol 2021 11 24;95:105092. Epub 2021 Sep 24.

Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France; IHU-Méditerranée Infection, Marseille, France. Electronic address:

Objectives: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille.

Methods: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death.

Results: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others.

Conclusion: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2021.105092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462069PMC
November 2021

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

Rev Cardiovasc Med 2021 09;22(3):1063-1072

Service de Cardiologie, Centre Hospitalier Universitaire La Timone, Assistance Publique Hôpitaux de Marseille, Aix Marseille Univ, C2VN, 13005 Marseille, France.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.31083/j.rcm2203116DOI Listing
September 2021

Incomplete tricarboxylic acid cycle and proton gradient in Pandoravirus massiliensis: is it still a virus?

ISME J 2021 Sep 23. Epub 2021 Sep 23.

Aix Marseille Univ, IRD, MEPHI, Marseille, France.

The discovery of Acanthamoeba polyphaga Mimivirus, the first isolated giant virus of amoeba, challenged the historical hallmarks defining a virus. Giant virion sizes are known to reach up to 2.3 µm, making them visible by optical microscopy. Their large genome sizes of up to 2.5 Mb can encode proteins involved in the translation apparatus. We have investigated possible energy production in Pandoravirus massiliensis. Mitochondrial membrane markers allowed for the detection of a membrane potential in purified virions and this was enhanced by a regulator of the tricarboxylic acid cycle but abolished by the use of a depolarizing agent. Bioinformatics was employed to identify enzymes involved in virion proton gradient generation and this approach revealed that eight putative P. massiliensis proteins exhibited low sequence identities with known cellular enzymes involved in the universal tricarboxylic acid cycle. Further, all eight viral genes were transcribed during replication. The product of one of these genes, ORF132, was cloned and expressed in Escherichia coli, and shown to function as an isocitrate dehydrogenase, a key enzyme of the tricarboxylic acid cycle. Our findings show for the first time that a membrane potential can exist in Pandoraviruses, and this may be related to tricarboxylic acid cycle. The presence of a proton gradient in P. massiliensis makes this virus a form of life for which it is legitimate to ask the question "what is a virus?".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41396-021-01117-3DOI Listing
September 2021

Whole Genome Sequencing of SARS-CoV-2 Strains in COVID-19 Patients From Djibouti Shows Novel Mutations and Clades Replacing Over Time.

Front Med (Lausanne) 2021 1;8:737602. Epub 2021 Sep 1.

IHU Méditerranée Infection, Marseille, France.

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.737602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440879PMC
September 2021

Monitoring the Circulation of SARS-CoV-2 Variants by Genomic Analysis of Wastewater in Marseille, South-East France.

Pathogens 2021 Aug 17;10(8). Epub 2021 Aug 17.

Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), Aix-Marseille University, 13005 Marseille, France.

The monitoring of SARS-CoV-2 RNA in sewage has been proposed as a simple and unbiased means of assessing epidemic evolution and the efficiency of the COVID-19 control measures. The past year has been marked by the emergence of variants that have led to a succession of epidemic waves. It thus appears that monitoring the presence of SARS-CoV-2 in wastewater alone is insufficient, and it may be important in the future to also monitor the evolution of these variants. We used a real-time RT-PCR screening test for variants in the wastewater of our city to assess the effectiveness of direct SARS-CoV-2 sequencing from the same wastewater. We compared the genome sequencing results obtained over the large RS network and the smaller B7 network with the different distributions of the variants observed by RT-PCR screening. The prevalence of the "UK variant" in the RS and B7 networks was estimated to be 70% and 8% using RT-PCR screening compared to 95% and 64% using genome sequencing, respectively. The latter values were close to the epidemiology observed in patients of the corresponding area, which were 91% and 58%, respectively. Genome sequencing in sewage identified SARS-CoV-2 of lineage B.1.525 in B7 at 27% (37% in patients), whereas it was completely missed by RT-PCR. We thus determined that direct sequencing makes it possible to observe, in wastewater, a distribution of the variants comparable to that revealed by genomic monitoring in patients and that this method is more accurate than RT-PCR. It also shows that, rather than a single large sample, it would be preferable to analyse several targeted samples if we want to more appropriately assess the geographical distribution of the different variants. In conclusion, this work supports the wider surveillance of SARS-CoV-2 variants in wastewater by genome sequencing and targeting small areas on the condition of having a sequencing capacity and, when this is not the case, to developing more precise screening tests based on the multiplexed detection of the mutations of interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10081042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401729PMC
August 2021

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants.

J Clin Med 2021 Jul 24;10(15). Epub 2021 Jul 24.

IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10153276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348317PMC
July 2021

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.

J Clin Med 2021 Jul 21;10(15). Epub 2021 Jul 21.

IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.

The 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10153210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348674PMC
July 2021

Epidemiological and genetic characterization of measles virus circulating strains at Marseille, France during 2017-2019 measles outbreak.

J Infect 2021 09 24;83(3):361-370. Epub 2021 Jul 24.

IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, Marseille 13005, France; MEPHI, Institut de Recherche pour le Développement (IRD), Aix-Marseille Universite, Marseille, France; Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, France. Electronic address:

Objectives: We attempted to establish a molecular investigation by Next Generation sequencing of the measles virus (MeV) strains circulating in Marseille-France during the last outbreak that occurred between 2017 and 2019.

Methods: The circulating MeV were isolated from clinical samples using cell culture method and whole genomes were sequenced by Illumina Miseq Next Generation. Genotyping and comparative analyses were assessed by phylogenetic reconstructions. Clinical and epidemiological data from cases were also recorded.

Results: A total of 110 MeV strains were isolated in cell culture. Our analysis based on whole genome sequences of 98 isolates confirmed that 93 strains belonged to the genotype D8 and 5 to the genotype B3. Phylogenetic analyses revealed 4 distinct MeV circulating clones in Marseille. Measles mostly occured in children < 5 years-old and in adults 30-50 years-old. Measles infection also occurred in 2 adequately vaccinated cases (2 doses). Among 63 measles cases of whom we had available clinical data informations, a total of 35 patients were hospitalized and 19 developed complications including one death case recorded.

Conclusions: Whole Genome Sequencing seems to be a useful tool for more refined genomic characterization of large measles outbreak. Vaccination strategies for measles eradication need to be re-evaluated in the current context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2021.07.011DOI Listing
September 2021

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

J Clin Med 2021 Jun 30;10(13). Epub 2021 Jun 30.

IHU Méditerranée Infection, 13005 Marseille, France.

(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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10132942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268313PMC
June 2021

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence.

J Clin Med 2021 Jun 15;10(12). Epub 2021 Jun 15.

IRD, AP-HM, SSA, VITROME, Aix Marseille University, 13005 Marseille, France.

Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro.

Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar.

Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory.

Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10122635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232800PMC
June 2021

Marseilleviruses: An Update in 2021.

Front Microbiol 2021 2;12:648731. Epub 2021 Jun 2.

IHU Méditerranée Infection, Marseille, France.

The family was the second family of giant viruses that was described in 2013, after the family . , isolated in 2007 by coculture on , is the prototype member of this family. Afterward, the worldwide distribution of marseilleviruses was revealed through their isolation from samples of various types and sources. Thus, 62 were isolated from environmental water, one from soil, one from a dipteran, one from mussels, and two from asymptomatic humans, which led to the description of 67 marseillevirus isolates, including 21 by the IHU Méditerranée Infection in France. Recently, five marseillevirus genomes were assembled from deep sea sediment in Norway. Isolated marseilleviruses have ≈250 nm long icosahedral capsids and 348-404 kilobase long mosaic genomes that encode 386-545 predicted proteins. Comparative genomic analyses indicate that the family includes five lineages and possesses a pangenome composed of 3,082 clusters of genes. The detection of marseilleviruses in both symptomatic and asymptomatic humans in stool, blood, and lymph nodes, and an up-to-30-day persistence of marseillevirus in rats and mice, raise questions concerning their possible clinical significance that are still under investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.648731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208085PMC
June 2021

Diverse Trajectories Drive the Expression of a Giant Virus in the Oomycete Plant Pathogen .

Front Microbiol 2021 1;12:662762. Epub 2021 Jun 1.

INRAE, Université Côte d'Azur, CNRS, ISA, Sophia Antipolis, France.

Giant viruses of amoebas, recently classified in the class Megaviricetes, are a group of viruses that can infect major eukaryotic lineages. We previously identified a set of giant virus sequences in the genome of , an oomycete and a devastating major plant pathogen. How viral insertions shape the structure and evolution of the invaded genomes is unclear, but it is known that the unprecedented functional potential of giant viruses is the result of an intense genetic interplay with their hosts. We previously identified a set of giant virus sequences in the genome of , an oomycete and a devastating major plant pathogen. Here, we show that viral pieces are found in a 550-kb locus and are organized in three main clusters. Viral sequences, namely RNA polymerases I and II and a major capsid protein, were identified, along with orphan sequences, as a hallmark of giant viruses insertions. Mining of public databases and phylogenetic reconstructions suggest an ancient association of oomycetes and giant viruses of amoeba, including faustoviruses, African swine fever virus (ASFV) and pandoraviruses, and that a single viral insertion occurred early in the evolutionary history of oomycetes prior to the - radiation, estimated at ∼80 million years ago. Functional annotation reveals that the viral insertions are located in a gene sparse region of the genome, characterized by a plethora of transposable elements (TEs), effectors and other genes potentially involved in virulence. Transcription of viral genes was investigated through analysis of RNA-Seq data and qPCR experiments. We show that most viral genes are not expressed, and that a variety of mechanisms, including deletions, TEs insertions and RNA interference may contribute to transcriptional repression. However, a gene coding a truncated copy of RNA polymerase II along a set of neighboring sequences have been shown to be expressed in a wide range of physiological conditions, including responses to stress. These results, which describe for the first time the endogenization of a giant virus in an oomycete, contribute to challenge our view of evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.662762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204020PMC
June 2021

Rhizomal Reclassification of Living Organisms.

Int J Mol Sci 2021 May 26;22(11). Epub 2021 May 26.

IHU Méditerranée Infection, 13005 Marseille, France.

Living organisms interact with each other during their lifetime, leading to genomes rearrangement and sequences transfer. These well-known phenomena give these organisms mosaic genomes, which challenge their classification. Moreover, many findings occurred between the IXXth and XXIst century, especially the discovery of giant viruses and candidate phyla radiation (CPR). Here, we tried to provide an updated classification, which integrates 216 representative genomes of the current described organisms. The reclassification was expressed through a genetic network based on the total genomic content, not on a single gene to represent the tree of life. This rhizomal exploration represents, more accurately, the evolutionary relationships among the studied species. Our analyses show a separated branch named fifth TRUC (Things Resisting Uncompleted Classifications). This taxon groups CPRs together, independently from Bacteria, Archaea (which regrouped also Nanoarchaeota and Asgard members), Eukarya, and the giant viruses (recognized recently as fourth TRUC). Finally, the broadening of analysis methods will lead to the discovery of new organisms, which justify the importance of updating the classification at every opportunity. In this perspective, our pragmatic representation could be adjusted along with the progress of evolutionary studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22115643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199106PMC
May 2021

Direct Diagnosis of Echovirus 12 Meningitis Using Metagenomic Next Generation Sequencing.

Pathogens 2021 May 17;10(5). Epub 2021 May 17.

IHU Méditerranée Infection, 13005 Marseille, France.

The current point-of-care diagnosis of enterovirus meningitis does not identify the viral genotype, which is prognostic. In this case report, more than 81% of an 12 genome were detected and identified by metagenomic next-generation sequencing, directly from the cerebrospinal fluid collected in a 6-month-old child with meningeal syndrome and meningitis: introducing 12 as an etiological agent of acute meningitis in the pediatric population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10050610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156364PMC
May 2021

SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment.

Viruses 2021 05 12;13(5). Epub 2021 May 12.

Aix Marseille University, IRD, AP-HM, MEPHI, 13005 Marseille, France.

SARS-CoV-2 nasopharyngeal shedding contributes to the spread of the COVID-19 epidemic. Among 3271 COVID-19 patients treated at the Hospital University Institute Méditerranée Infection, Marseille, France from 3 March to 27 April 2020, tested at least twice by qRT-PCR, the median SARS-CoV-2 nasopharyngeal shedding duration was 6 days (range 2-54 days). Compared with short shedders (qRT-PCR positivity < 10 days), 34 (1.04%) persistent shedders (qRT-PCR positivity ≥ 17 days; mean ± SD: 23.3 ± 3.8 days) were significantly older, with associated comorbidities, exhibiting lymphopenia, eosinopenia, increased D-dimer and increased troponin ( < 0.05), and were hospitalized in intensive care unit in 17.7% vs. 1.1% of cases ( < 0.0001). Viral culture was positive in six persistent shedders after day 10, including in one patient after day 17, and no viral co-pathogen was detected in 33 tested patients. Persistent shedders received azithromycin plus hydroxychloroquine ≥ 3 days in 26/34 (76.5%) patients, a figure significantly lower than in short shedders (86.6%) ( = 0.042). Accordingly, mortality was 14.7% vs. 0.5% ( < 0.0001). Persistent shedding was significantly associated with persistent dyspnea and anosmia/ageusia ( < 0.05). In the context of COVID-19 treatment, including treatment with azithromycin plus hydroxychloroquine, the persistence of SARS-CoV-2 nasopharyngeal shedding was a rare event, most frequently encountered in elderly patients with comorbidities and lacking azithromycin plus hydroxychloroquine treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13050890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150993PMC
May 2021

Extensive Comparative Genomic Analysis of and Reveals a Direct Association between the Absence of CRISPR-Cas Systems, the Presence of Anti-Endonuclease (ardA) and the Acquisition of Vancomycin Resistance in .

Microorganisms 2021 05 21;9(6). Epub 2021 May 21.

Aix Marseille University, IRD, APHM, MEPHI, IHU-Mediterranee Infection, 13005 Marseille, France.

Here, we performed a comparative genomic analysis of all available genomes of ( = 1591) and ( = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of antimicrobial resistance, especially vancomycin resistance genes. Most of the analysed Enterococci were isolated from humans and less than 14% of them were from foods and animals. We analysed and detected CRISPR-Cas systems in 75.36% of genomes and only 4.89% of genomes with a significant difference (-value < 10). We found a negative correlation between the number of CRISPR-Cas systems and genome size (r = -0.397, -value < 10) and a positive correlation between the genome %GC content and the number of CRISPR-Cas systems (r = 0.215, -value < 10). Our findings showed that the presence of the anti-endonuclease gene may explain the decrease in the number of CRISPR-Cas systems in , known to deactivate the endonucleases' protective activities and enable the genome to be versatile in acquiring mobile genetic elements, including carriers of antimicrobial resistance genes, especially . Most importantly, we observed that there was a direct association between the absence of CRISPR-Cas, the presence of the anti-CRISPR gene and the acquisition of vancomycin resistance genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9061118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224324PMC
May 2021

Clinical outcomes in COVID-19 patients infected with different SARS-CoV-2 variants in Marseille, France.

Clin Microbiol Infect 2021 Oct 24;27(10):1516.e1-1516.e6. Epub 2021 May 24.

Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France; Institut Hospitalo-Universitaire-Méditerranée Infection, Marseille, France. Electronic address:

Objectives: To compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021.

Methods: In this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all).

Results: A total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively).

Conclusions: The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2021.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142822PMC
October 2021
-->