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1.
Clin Infect Dis ; 74(4): 707-710, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703814

ABSTRACT

There are concerns about neutralizing antibodies' (NAbs') potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2/genetics , United Kingdom/epidemiology
2.
Viruses ; 14(2)2022 01 24.
Article in English | MEDLINE | ID: covidwho-1650825

ABSTRACT

We explored the molecular evolution of the spike gene after the administration of anti-spike monoclonal antibodies in patients with mild or moderate forms of COVID-19. Four out of the 13 patients acquired a mutation during follow-up; two mutations (G1204E and E406G) appeared as a mixture without clinical impact, while the Q493R mutation emerged in two patients (one receiving bamlanivimab and one receiving bamlanivimab/etesevimab) with fatal outcomes. Careful virological monitoring of patients treated with mAbs should be performed, especially in immunosuppressed patients.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/therapy , Evolution, Molecular , Immune Evasion , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/immunology , Drug Combinations , Female , Humans , Immunotherapy/statistics & numerical data , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
3.
Sci Rep ; 12(1): 1094, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1634513

ABSTRACT

France went through three deadly epidemic waves due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing major public health and socioeconomic issues. We proposed to study the course of the pandemic along 2020 from the outlook of two major Parisian hospitals earliest involved in the fight against COVID-19. Genome sequencing and phylogenetic analysis were performed on samples from patients and health care workers (HCWs) from Bichat (BCB) and Pitié-Salpêtrière (PSL) hospitals. A tree-based phylogenetic clustering method and epidemiological data were used to investigate suspected nosocomial transmission clusters. Clades 20A, 20B and 20C were prevalent during the spring wave and, following summer, clades 20A.EU2 and 20E.EU1 emerged and took over. Phylogenetic clustering identified 57 potential transmission clusters. Epidemiological connections between participants were found for 17 of these, with a higher proportion of HCWs. The joint presence of HCWs and patients suggest viral contaminations between these two groups. We provide an enhanced overview of SARS-CoV-2 phylogenetic changes over 2020 in the Paris area, one of the regions with highest incidence in France. Despite the low genetic diversity displayed by the SARS-CoV-2, we showed that phylogenetic analysis, along with comprehensive epidemiological data, helps to identify and investigate healthcare associated clusters.


Subject(s)
COVID-19 , Genome, Viral , Phylogeny , SARS-CoV-2/genetics , Adult , Aged , COVID-19/epidemiology , COVID-19/genetics , COVID-19/transmission , Female , Humans , Male , Middle Aged , Paris/epidemiology , Retrospective Studies
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295413

ABSTRACT

ABSTRACT There are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, most of the sera harbored at least a NAb titer ≥ 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.

5.
Clin Infect Dis ; 73(7): e1762-e1765, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455264

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.


Subject(s)
COVID-19 , RNA-Dependent RNA Polymerase , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , B-Lymphocytes , COVID-19/drug therapy , COVID-19/therapy , Female , Humans , Immunization, Passive , Mutation , SARS-CoV-2
8.
Clin Infect Dis ; 74(4): 707-710, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1246701

ABSTRACT

There are concerns about neutralizing antibodies' (NAbs') potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2/genetics , United Kingdom/epidemiology
10.
Nat Commun ; 12(1): 844, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1069105

ABSTRACT

There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , Binding Sites/immunology , COVID-19/virology , Cell Line, Tumor , Female , Humans , Immunoglobulin A/immunology , Male , Middle Aged , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Time Factors
12.
J Clin Virol ; 130: 104573, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-701949

ABSTRACT

BACKGROUND: RT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas® (Roche) and the RealStar® assay (Altona). METHODS: Assessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas® assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMérieux). RESULTS: Overall, the agreement (positive for at least one gene) was 76 %. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99 %. Regarding the positive Ct values, linear regression analysis showed a coefficient of determination (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct. CONCLUSIONS: In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar® assay, probably due to a low viral load close to the detection limit of both assays.


Subject(s)
Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Molecular Diagnostic Techniques/methods , Pneumonia, Viral/diagnosis , Reverse Transcriptase Polymerase Chain Reaction , Betacoronavirus , COVID-19 , COVID-19 Testing , Humans , Limit of Detection , Pandemics , Prospective Studies , Reagent Kits, Diagnostic , SARS-CoV-2 , Sensitivity and Specificity , Viral Load , Viral Proteins/genetics
13.
Clin Microbiol Infect ; 26(11): 1560.e1-1560.e4, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-670663

ABSTRACT

OBJECTIVES: Studies are needed to better understand the genomic evolution of the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to describe genomic diversity of SARS-CoV-2 by next-generation sequencing (NGS) in a patient with longitudinal follow-up for SARS-CoV-2 infection. METHODS: Sequential samples collected between January 29th and February 4th, 2020, from a patient infected by SARS-CoV-2 were used to perform amplification of two genome fragments-including genes encoding spike, envelope, membrane and nucleocapsid proteins-and NGS was carried out with Illumina® technology. Phylogenetic analysis was performed with PhyML and viral variant identification with VarScan. RESULTS: Majority consensus sequences were identical in most of the samples (5/7) and differed in one synonymous mutation from the Wuhan reference sequence. We identified 233 variants; each sample harboured in median 38 different minority variants, and only four were shared by different samples. The frequency of mutation was similar between genes and correlated with the length of the gene (r = 0.93, p = 0.0002). Most of mutations were substitution variations (n = 217, 93.1%) and about 50% had moderate or high impact on gene expression. Viral variants also differed between lower and upper respiratory tract samples collected on the same day, suggesting independent sites of replication of SARS-CoV-2. CONCLUSIONS: We report for the first time minority viral populations representing up to 1% during the course of SARS-CoV-2 infection. Quasispecies were different from one day to the next, as well as between anatomical sites, suggesting that in vivo this new coronavirus appears as a complex and dynamic distributions of variants.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Quasispecies/genetics , Betacoronavirus/classification , COVID-19 , Follow-Up Studies , Genome, Viral/genetics , Humans , Mutation , Pandemics , Phylogeny , SARS-CoV-2 , Viral Proteins/genetics
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