Publications by authors named "Karen Zafilaza"

Objectives: Mutational dynamics of SARS-CoV-2 in immunocompromised hosts, although well documented, remain a relatively unexplored mechanism. This study aims to compare the viral replication load and genetic diversity of SARS-CoV-2 in immunocompromised patients and non-immunocompromised individuals (NICs) from two major hospitals in Paris from January 2021 to May 2023.

Methods: Cycle threshold (CT) values were measured by TaqPath COVID-19 RT-PCR (Thermo Fisher Scientific).

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Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors.

Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021).

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The goal of this study is to test a novel device and methodology based on the "Pebble" platform and real-time quantitative colorimetric loop-mediated isothermal amplification (qcLAMP) during SARS-CoV-2 detection using crude samples and extracted RNA. The new method employs an inexpensive lightweight device aimed toward rapid point-of-care testing. An extensive evaluation was performed consisting of 1,693 clinical samples across five independent clinical testing centers.

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Background: High-risk patients, often immunocompromised and not responding to vaccine, continue to experience severe coronavirus disease 2019 (COVID-19) and death. Monoclonal antibodies (mAbs) were shown to be effective to prevent severe COVID-19 for these patients. Nevertheless, concerns about the emergence of resistance mutations were raised.

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Article Synopsis
  • Immunocompromised individuals tend to experience longer SARS-CoV-2 infections, increasing the chances for new mutations, especially in the spike protein, which is important for vaccines.
  • A study in Paris analyzed samples from 444 immunocompromised patients and 234 healthcare workers, finding greater genetic diversity of the virus in the immunocompromised group.
  • The research indicated that mutations in the viruses from immunocompromised patients contributed to the evolution of new variants, suggesting potential concerns for immune response and severity of future infections.
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Antibodies effective against the recent Omicron sublineages are missing. By taking advantage of a multi-centric prospective cohort of immunocompromised individuals treated for mild-to-moderate COVID-19, Bruel et al. show that administration of 500 mg of sotrovimab induces serum neutralization and antibody-dependent cellular cytotoxicity of BQ.

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  • The study aimed to assess the vaccine response in multiple sclerosis (MS) patients treated with anti-CD20, specifically looking at the effects of an enhanced BNT162b2 vaccine regimen on their immune response to SARS-CoV-2.
  • Results showed that patients on anti-CD20 had significantly lower seropositivity and neutralization activity after vaccination compared to those on other MS treatments, especially against the Omicron variant.
  • A delayed booster vaccination did improve seropositivity in anti-CD20 patients, but their neutralizing response remained notably weak compared to patients receiving other therapies.
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Although France was one of the most affected European countries by the COVID-19 pandemic in 2020, the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) movement within France, but also involving France in Europe and in the world, remain only partially characterized in this timeframe. Here, we analyzed GISAID deposited sequences from January 1 to December 31, 2020 ( = 638,706 sequences at the time of writing). To tackle the challenging number of sequences without the bias of analyzing a single subsample of sequences, we produced 100 subsamples of sequences and related phylogenetic trees from the whole dataset for different geographic scales (worldwide, European countries, and French administrative regions) and time periods (from January 1 to July 25, 2020, and from July 26 to December 31, 2020).

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Article Synopsis
  • SARS-CoV-2, the virus that causes COVID-19, has a Spike protein that binds to the ACE2 receptor and is critical for the virus's interaction with the immune system.
  • Mutations in the Spike protein lead to different variants, each with unique traits regarding how easily they spread, their severity, and their ability to evade immune responses.
  • Since early 2021, several variants have emerged, with notable lineage changes indicating a rapid evolution of SARS-CoV-2, resulting in increased transmissibility and immune evasion capabilities.
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  • - The study aimed to compare the outcomes of patients infected with Omicron BA.1 and BA.2 who were treated with either sotrovimab or nirmatrelvir to prevent severe COVID-19.
  • - Of the 255 patients analyzed, nirmatrelvir resulted in faster negative PCR conversion (4 days) compared to sotrovimab (11.5 days), and a lower hospitalization rate was observed in nirmatrelvir-treated patients.
  • - The findings suggest that nirmatrelvir may lead to quicker viral clearance than sotrovimab in high-risk patients, potentially reducing the spread of the virus.
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  • * Recovered COVID-19 patients who received one vaccine dose showed the strongest neutralizing response, while vaccinated naïve patients had high levels against earlier variants but lower activity against the Omicron variant.
  • * The surrogate assays demonstrated a good correlation with VNT results, indicating they could serve as reliable alternatives for analyzing neutralization capabilities on a larger scale, especially against resistant variants like Beta and Omicron.
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  • Large-scale screening for SARS-CoV-2 is crucial for controlling outbreaks, but new variants like Delta and Omicron may affect the reliability of rapid diagnostic tests (RDTs).
  • A study compared clinical and virological data from Delta and Omicron infections and found that the sensitivity of RDTs was significantly lower for Omicron (53.8%) compared to Delta (74.7%).
  • The research revealed that higher viral loads (VL) were present in Delta cases, which correlated with better test performance, suggesting that RDT sensitivity varies based on the variant, and repeated testing may be necessary if Omicron is suspected.
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  • The study examined healthcare-associated COVID-19 (HA-COVID-19) from September to November 2020 at Sorbonne University Hospital, revealing 209 reported cases and a significant mortality rate of 31.5% among HA-COVID-19 patients.
  • The incidence of HA-COVID-19 was closely linked to community-associated cases (CA-COVID-19) and infections among healthcare workers (HCWs), indicating considerable nosocomial transmission.
  • Whole-genome sequencing (WGS) played a crucial role in cluster investigations, helping to identify transmission routes and excluding a third of initially assigned cases, thus aiding in enhancing infection prevention and control strategies.
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Objectives: To assess humoral responses to SARS-CoV-2 Delta-variant in people with HIV (PWH) after BNT162b2-vaccination.

Design: Multicenter cohort study of PWH with CD4 + cell count less than 500 cells/μl and viral load less than 50 copies/ml on stable antiretroviral therapy for at least 3 months.

Methods: Anti-SARS-CoV-2 receptor-binding-domain IgG antibodies (anti-RBD IgG) were quantified and neutralization capacity was evaluated by ELISA/GenScript and virus-neutralization-test against the D614G-strain, beta and delta variants before vaccination (day 0) and 1 month after complete schedule (M1).

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Objective: We aimed to characterize the evolution of humoral immune response up to 1 year after SARS-CoV-2 infection in healthcare workers (HCWs) during the first wave of COVID-19 in Paris.

Methods: Serum samples from 92 HCWs were tested at month 0 (M0), M6, and M12 after SARS-CoV-2 infection for IgG targeting the nucleocapsid (N), IgG targeting the receptor-binding domain (RBD) of spike (S) protein, IgA targeting S, and anti-RBD neutralizing antibodies. After M6, 46 HCWs received a single dose of COVID-19 vaccine.

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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.

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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.

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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.

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