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1.
Frontiers in microbiology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1696164

ABSTRACT

After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314917

ABSTRACT

Background: From mid-March to mid-April 2020, the French aircraft carrier Charles de Gaulle suffered a COVID-19 outbreak. An investigation was performed to describe the outbreak, including how the virus was introduced on board. We present the clinical pictures of COVID-19 cases with risk factors for infection and severity, effectiveness of preventive measures, and we discuss the real collective protective rate.Methods: A confirmed case was any service member with a positive SARS-CoV-2 RT-PCR and/or who presented symptoms of anosmia and/or ageusia. We considered the entire crew as a cohort and questioned them about individual, epidemiological, and clinical data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.Results: The attack rate was 65% (1085/1767). The sex ratio was 6·9, and median age was 29 years. There were four clinical profiles: asymptomatic (13·0%), non-specific symptomatic (8·1%), specific symptomatic (76·3%), and severe (i.e. requiring oxygen therapy, 2·6%). Active smoking prevented severe COVID-19;age and obesity were risk factors.The instantaneous reproduction rate Rt and viral sequencing supported the hypothesis of several introductions of the virus on board, with an acceleration of the Rt when preventive measures were lifted. Physical distancing prevented infection (ORa, 0·55, 95% CI, 0·40-0·76). In the end, transmission stopped when the proportion of infected personnel was large enough to prevent the virus from circulating (65%, 95% CI, 62-68).Discussion: Asymptomatic and non-specific clinical pictures of COVID-19, combined with a lack of knowledge at that time about the specific symptoms of COVID-19 (anosmia, ageusia), delayed detection of the outbreak. Once it was identified, the lack of an isolation ward made it difficult to manage transmission on board, and the outbreak spread until a collective protective rate was reached. However, physical distancing was effective when applied. Syndromic surveillance and point-of-care biology could enable early detection of such viral emergences or outbreaks.Funding Information: No funding to declare.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This was not an experimental protocol, but an outbreak investigation with routine care provided to infected individuals, so no ethical approval from any named institutional and/or licensing/ethics committee was required. We obtained individual informed consent to analyze data. No administrative authorization was required to access and use medical records. We chose not to provide certain details and to aggregate certain data in order to maintain patient anonymity. All methods were carried out in accordance with relevant guidelines and regulations.

3.
Front Microbiol ; 12: 796807, 2021.
Article in English | MEDLINE | ID: covidwho-1674356

ABSTRACT

From January 18th to August 13th, 2021, 13,804 unvaccinated and 1,156 patients who had received at least one COVID-19 vaccine dose were tested qPCR-positive for SARS-CoV-2 in our center. Among vaccinated patients, 949, 205 and 2 had received a single, two or three vaccine doses, respectively. Most patients (80.3%) had received the Pfizer-BioNTech vaccine. The SARS-CoV-2 variants infecting vaccinated patients varied over time, reflecting those circulating in the Marseille area, with a predominance of the Marseille-4/20A.EU2 variant from weeks 3 to 6, of the Alpha/20I variant from weeks 7 to 25, and of the Delta/21A variant from week 26. SARS-CoV-2 infection was significantly more likely to occur in the first 13 days post-vaccine injection in those who received a single dose (48.9%) than two doses (27.4%, p< 10-3). Among 161 patients considered as fully vaccinated, i.e., >14 days after the completion of the vaccinal scheme (one dose for Johnson and Johnson and two doses for Pfizer/BioNTech, Moderna and Sputnik vaccines), 10 (6.2%) required hospitalization and four (2.5%) died. Risks of complications increased with age in a nonlinear pattern, with a first breakpoint at 54, 33, and 53 years for death, transfer to ICU, and hospitalization, respectively. Among patients infected by the Delta/21A or Alpha/20I variants, partial or complete vaccination exhibited a protective effect with a risk divided by 3.1 for mortality in patients ≥ 55 years, by 2.8 for ICU transfer in patients ≥ 34 years, and by 1.8 for hospitalization in patients ≥ 54 years. Compared to partial vaccination, complete vaccination provided an even stronger protective effect, confirming effectiveness to prevent severe forms of COVID-19.

4.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1439023

ABSTRACT

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], I2 = 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.


Subject(s)
Ambulatory Care , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Early Medical Intervention , Hydroxychloroquine/therapeutic use , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Drug Therapy, Combination , Female , France , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Outpatients , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Young Adult
5.
J Clin Med ; 10(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1403797

ABSTRACT

(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.

6.
Int J Infect Dis ; 96: 154-156, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1385692

ABSTRACT

Respiratory viruses are a major cause of mortality worldwide and in France, where they cause several thousands of deaths every year. University Hospital Institute-Méditerranée Infection performs real-time surveillance of all diagnoses of infections and associated deaths in public hospitals in Marseille, Southeastern France. This study compared mortality associated with diagnoses of respiratory viruses during the colder months of 2018-2019 and 2019-2020 (week 47-week 14). In 2018-2019, 73 patients (0.17% of 42,851 hospitalized patients) died after being diagnosed with a respiratory virus; 40 and 13 deaths occurred in patients diagnosed with influenza A virus and respiratory syncytial virus (RSV), respectively. In 2019-2020, 50 patients (0.10% of 49,043 patients hospitalized) died after being diagnosed with a common respiratory virus; seven and seven deaths occurred in patients diagnosed with influenza A virus and RSV, respectively. Additionally, 55 patients died after being diagnosed with SARS-CoV-2. The proportion of respiratory virus-associated deaths among hospitalized patients was thus significantly lower for common respiratory viruses in 2019-2020 than in 2018-2019 (102 versus 170 per 100,000 hospitalized patients; p = 0.003), primarily as a consequence of a decrease in influenza A virus (-83%) and RSV (-46%)-associated deaths. Overall, the proportion of respiratory virus-associated deaths among hospitalized patients was higher, but not significantly, in 2019-2020 than in 2018-2019 (214 versus 170 per 100,000 hospitalized patients; p = 0.08, Yates-corrected Chi-square test). These findings put into perspective the death burden of SARS-CoV-2 infections in this geographical area.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Influenza A virus , Influenza, Human/epidemiology , Pneumonia, Viral/mortality , Respiratory Syncytial Virus Infections/epidemiology , COVID-19 , Child, Preschool , Female , France/epidemiology , Humans , Infant , Male , Middle Aged , Pandemics , SARS-CoV-2 , Time Factors
7.
J Clin Med ; 10(15)2021 Jul 21.
Article in English | MEDLINE | ID: covidwho-1325710

ABSTRACT

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.

8.
Saf Sci ; 140: 105296, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1301014

ABSTRACT

In late 2019, an epidemic of SARS-CoV-2 broke out in central China. Within a few months, this new virus had spread right across the globe, officially being classified as a pandemic on 11 March 2020. In France, which was also being affected by the virus, the government applied specific epidemiological management strategies and introduced unprecedented public health measures. This article describes the outbreak management system that was applied within the French military and, more specifically, analyzes an outbreak of COVID-19 that occurred on board a nuclear aircraft carrier. We applied the AcciMap systemic analysis approach to understand the course of events that led to the outbreak and identify the relevant human and organizational failures. Results highlight causal factors at several levels of the outbreak management system. They reveal problems with the benchmarks used for diagnosis and decision-making, and underscore the importance of good communication between different levels. We discuss ways of improving epidemiological management in military context.

9.
Front Microbiol ; 12: 664477, 2021.
Article in English | MEDLINE | ID: covidwho-1256387

ABSTRACT

In recent years, and more specifically at the beginning of the COVID-19 crisis, wastewater surveillance has been proposed as a tool to monitor the epidemiology of human viral infections. In the present work, from July to December 2020, the number of copies of SARS-CoV-2 RNA in Marseille's wastewater was correlated with the number of new positive cases diagnosed in our Institute of Infectious Disease, which tested about 20% of the city's population. Number of positive cases and number of copies of SARS-CoV-2 RNA in wastewater were significantly correlated (p = 0.013). During the great epidemic peak, from October to December 2020, the curves of virus in the sewers and the curves of positive diagnoses were perfectly superposed. During the summer period, the superposition of curves was less evident as subject to many confounding factors that were discussed. We also tried to correlate the effect of viral circulation in wastewater with containment measures, probably the most unbiased correlation on their potential inflection effect of epidemic curves. Not only is this correlation not obvious, but it also clearly appears that the drop in cases as well as the drop in the viral load in the sewers occur before the containment measures. In fact, this suggests that there are factors that initiate the end of the epidemic peak independently of the containment measure. These factors will therefore need to be explored more deeply in the future.

10.
Clin Microbiol Infect ; 27(10): 1516.e1-1516.e6, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1240263

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Child , Child, Preschool , Female , France/epidemiology , Genotype , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units , Male , Middle Aged , Odds Ratio , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , Severity of Illness Index , Young Adult
12.
Travel Med Infect Dis ; 40: 101980, 2021.
Article in English | MEDLINE | ID: covidwho-1096252

ABSTRACT

BACKGROUND: In Marseille, France, the COVID-19 incidence evolved unusually with several successive epidemic phases. The second outbreak started in July, was associated with North Africa, and involved travelers and an outbreak on passenger ships. This suggested the involvement of a new viral variant. METHODS: We sequenced the genomes from 916 SARS-CoV-2 strains from COVID-19 patients in our institute. The patients' demographic and clinical features were compared according to the infecting viral variant. RESULTS: From June 26th to August 14th, we identified a new viral variant (Marseille-1). Based on genome sequences (n = 89) or specific qPCR (n = 53), 142 patients infected with this variant were detected. It is characterized by a combination of 10 mutations located in the nsp2, nsp3, nsp12, S, ORF3a, ORF8 and N/ORF14 genes. We identified Senegal and Gambia, where the virus had been transferred from China and Europe in February-April as the sources of the Marseille-1 variant, which then most likely reached Marseille through Maghreb when French borders reopened. In France, this variant apparently remained almost limited to Marseille. In addition, it was significantly associated with a milder disease compared to clade 20A ancestor strains, in univariate analysis. CONCLUSION: Our results demonstrate that SARS-CoV-2 can genetically diversify rapidly, its variants can diffuse internationally and cause successive outbreaks.


Subject(s)
COVID-19/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , Africa South of the Sahara/epidemiology , Aged , Amino Acid Substitution , COVID-19/epidemiology , China/epidemiology , Coronavirus Papain-Like Proteases/genetics , Coronavirus RNA-Dependent RNA Polymerase/genetics , Female , France/epidemiology , Genome, Viral , Humans , Male , Middle Aged , Mutation , Phylogeny , Travel , Viral Nonstructural Proteins/genetics , Viral Proteins/genetics , Viroporin Proteins/genetics
13.
Int J Infect Dis ; 102: 17-19, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060100

ABSTRACT

OBJECTIVE: To describe the characteristics of COVID-19 patients seen in March-April and June-August 2020 in Marseille, France with the aim to investigate possible changes in the disease between these two time periods. METHODS: Demographics, hospitalization rate, transfer to intensive care unit (ICU), lethality, clinical and biological parameters were investigated. RESULTS: Compared to those seen in March-April, COVID-19 patients seen in June-August were significantly younger (39.2 vs. 45.3 years), more likely to be male (52.9% vs. 45.6%), and less likely to be hospitalized (10.7 vs. 18.0%), to be transferred to ICU (0.9% vs. 1.8%) and to die (0.1% vs. 1.1%). Their mean fibrinogen and D-dimer blood levels were lower (1.0 vs. 1.5 g/L and 0.6 vs. 1.1 µg/mL, respectively). By contrast, their viral load was higher (cycle threshold ≤16 = 5.1% vs. 3.7%). CONCLUSIONS: Patients in the two periods did not present marked age and sex differences, but markers of severity were undoubtedly less prevalent in the summer period, associating with a 10 times decrease in the lethality rate.


Subject(s)
COVID-19/epidemiology , Adult , Aged , COVID-19/blood , COVID-19/mortality , Disease Outbreaks , Female , Fibrin Fibrinogen Degradation Products/analysis , France/epidemiology , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2 , Seasons , Time Factors
15.
Int J Infect Dis ; 100: 88-94, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-943163

ABSTRACT

OBJECTIVES: We investigated possible COVID-19 epidemic clusters and their common sources of exposure that led to a sudden increase in the incidence of COVID-19 in the Jewish community of Marseille between March 15 and March 20, 2020. METHODS: All data were generated as part of routine work at Marseille university hospitals. Biological diagnoses were made by RT-PCR testing. A telephone survey of families in which a laboratory confirmed case was diagnosed was conducted to determine possible exposure events. RESULTS: As of March 30, 2020, 63 patients were linked to 6 epidemic clusters. The 6 clusters were linked to religious and social activities: a ski trip, organized meals for the Purim Jewish celebration in community and family settings on March 10, a religious service and a charity gala. Notably, 40% of the patients were infected by index patients during the presymptomatic period, which was 2.5 days before symptom onset. When considering household members, all 12 patients who tested negative and who did not develop any relevant clinical symptoms compatible with COVID-19 were 1-16 years of age. The clinical attack rate (symptoms compatible with COVID-19, and biologically confirmed by PCR) in adults was 85% compared to 26% in children. CONCLUSIONS: Family and community gatherings for the Purim Jewish celebration probably accelerated the spread of COVID-19 in the Marseille Jewish community, leading to multiple epidemic clusters. This investigation of family clusters suggested that all close contacts of patients with confirmed COVID-19 who were not infected were children.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Judaism , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Female , France/epidemiology , Humans , Infant , Male , Middle Aged , Pandemics , SARS-CoV-2 , Young Adult
16.
Int J Infect Dis ; 101: 121-125, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-797460

ABSTRACT

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 Méditerranée 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.


Subject(s)
Coronavirus/isolation & purification , SARS-CoV-2/isolation & purification , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , France , Humans , Infant , Infant, Newborn , Middle Aged , Young Adult
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