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252 Research products, page 1 of 26

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  • HAL - UPEC / UPEM
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  • Open Access
    Authors: 
    Sofía Jijón; Ahmad Al Shafie; Laura Temime; Kévin Jean; Mohamed El Kassas;
    Publisher: Cold Spring Harbor Laboratory
    Country: France

    ABSTRACTIn response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1-to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals.Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a model-based approach that accounts for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence of SARS-CoV-2 infection among HCWs. Over a total follow-up of 6,064 person-days (PD), we estimated an incidence rate (per 100 PD) of 1.05 (95% CrI: 0.58–1.65) at Hospital 1, 1.92 (95% CrI: 0.93–3.28) at Hospital 2 and 7.62 (95% CrI: 3.47–13.70) at Hospital 3. The probability for an HCW to be infected at the end of a shift was 13.7% (95% CrI: 7.8%–20.8%) and 23.8% (95% CrI: 12.2%–37.3%) for a 2-week shift at Hospital 1 and Hospital 2, respectively, which lies within the range of risk levels previously documented in standard healthcare settings, whereas it was >3-fold higher for a 7-day shift at Hospital 2 (42.6%, 95%CrI: 21.9%–64.4%). Our model-based estimates unveil a proportion of undiagnosed infections among HCWs of 46.4% (95% CrI: 18.8%–66.7%), 45.0% (95% CrI: 5.6%–70.8%) and 59.2% (95% CrI: 34.8%–78.8%), for Hospitals 1 to 3, respectively.The large variation in SARS-CoV-2 incidence we document here suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient anticipation and infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.WHAT THIS PAPER ADDSWhat is already known on this topicPrevious studies conducted in standard care settings have documented that frontline healthcare workers (HCWs) face high risk of COVID-19. Whether risk levels differ in alternative care models, such as COVID-19 quarantine hospitals in Egypt where HCWs resided in the hospital days and nights for various durations, is unknown.What this study addsCOVID-19 risk for HCWs in quarantine hospitals varies substantially between facilities, from risk levels that are in the range of those documented in standard healthcare settings to levels that were approximatively 3 times higher.How this study might affect research, practice or policyWith sufficient anticipation and infection control measures, occupational COVID-19 risk for HCWs working in quarantine hospitals can be brought down to levels similar to those observed in standard healthcare settings.

  • Open Access
    Authors: 
    Raffaele Brustia; Giuliana Amaddeo; Rami Rhaiem; Eric Levesque; Antoine Monsel; Vanessa Baaroun; Mylène Dimmock; Marc-Antoine Rousseau; Oriane Wagner-Ballon; Francoise Botterel; +2 more
    Publisher: Informa UK Limited
    Country: France

    International audience; Background: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support.Objective: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale.Design: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France.Results: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% (n = 3) and 22% (n = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively.Conclusions: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

  • Open Access English
    Authors: 
    Emmanuel Laplantine; Christine Chable-Bessia; Anne Oudin; Jitendryia Swain; Adèle Soria; Peggy Merida; Manon Gourdelier; Sarra Mestiri; Indira Besseghe; Erwan Bremaud; +11 more
    Publisher: HAL CCSD
    Country: France

    International audience; Patients with severe COVID-19 show an altered immune response that fails to control the viral spread and suffer from exacerbated inflammatory response, which eventually can lead to death. A major challenge is to develop an effective treatment for COVID-19. NF-κB is a major player in innate immunity and inflammatory process. By a high-throughput screening approach, we identified FDA-approved compounds that inhibit the NF-κB pathway and thus dampen inflammation. Among these, we show that Auranofin prevents post-translational modifications of NF-κB effectors and their recruitment into activating complexes in response to SARS-CoV-2 infection or cytokine stimulation. In addition, we demonstrate that Auranofin counteracts several steps of SARS-CoV-2 infection. First, it inhibits a raft-dependent endocytic pathway involved in SARS-CoV-2 entry into host cells; Second, Auranofin alters the ACE2 mobility at the plasma membrane. Overall, Auranofin should prevent SARS-CoV-2 infection and inflammatory damages, offering new opportunities as a repurposable drug candidate to treat COVID-19.

  • Open Access English
    Authors: 
    Charreire, Hélène; Verdot, Charlotte; Szabo de Edelenyi, Fabien; Deschasaux-Tanguy, Mélanie; Srour, Bernard; Druesne-Pecollo, Nathalie; Esseddik, Younes; Allès, Benjamin; Baudry, Julia; Deschamps, Valérie; +8 more
    Publisher: HAL CCSD
    Country: France

    International audience; Background: COVID-19 lockdowns represent natural experiments where limitations of movement impact on lifestyle behaviors. The aim of this paper was to assess how lockdowns have influenced physical activity and sedentary behaviors among French adults.Methods: 32,409 adults from the NutriNet-Santé study filled out questionnaires in April 2020 (the first 2 weeks after the start of lockdown) and in May 2020 (2 weeks before the lockdown ended). Participants were asked about changes in physical activity level and sitting time, types of physical activity performed, and main reasons for change.Results: For decreased physical activity, similar rates were found at the beginning and end of the lockdown (58 and 55%–56 and 53%, in women and men, respectively). For increased physical activity, the figures were lower (20 and 14%–23 and 18%, in women and men, respectively). The participants with a decreasing physical activity evolution were older and more likely to be living in urban areas. The main reasons for (i) decreased physical activity were limitations of movement and not liking indoor exercise, (ii) increased physical activity were to stay physically fit and healthy. Physical activity changes were inversely associated with reported depressive symptoms.Conclusions: Changes in physical activity and sedentary behaviors are heterogenous for both genders during the lockdown.

  • Open Access English
    Authors: 
    Ioana Brudasca; Quentin Lisan; Romain Tournegros; Moustafa Bensafi; Camille Ferdenzi; Arnaud Fournel; Luna Denoix; Stéphane Tringali; Maxime Fieux;
    Publisher: HAL CCSD
    Country: France

    International audience; Background: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.Methods:The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.Results: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).Conclusion: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.

  • Open Access
    Authors: 
    Timothée Bruel; Laurie Pinaud; Laura Tondeur; Delphine Planas; Isabelle Staropoli; Françoise Porrot; Florence Guivel-Benhassine; Mikaël Attia; Stéphane Pelleau; Tom Woudenberg; +12 more
    Publisher: Elsevier BV
    Country: France

    International audience; BACKGROUND: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.METHODS: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2(nd) and 3(rd) vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1.FINDINGS: Among the 38 elderly individuals recruited to the cohort study between November 23(rd), 2020 and April 29(th), 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively.INTERPRETATION: This study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity.

  • Open Access
    Authors: 
    Bastien Berger; Marc Hazzan; Nassim Kamar; Hélène Francois; Marie Matignon; Clarisse Greze; Philippe Gatault; Luc Frimat; Pierre F. Westeel; Valentin Goutaudier; +21 more
    Publisher: Elsevier BV
    Country: France

    International audience; SARS-CoV-2 pandemic evolved in two consecutive waves over 2020. Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear. In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48) and COVID-19 hospitalization period was not associated with death due to COVID in multivariate analysis (HR 0.89, 95% CI 0.67 - 1.17, p = 0.4). We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.

  • Open Access
    Authors: 
    Philippe-Henri Secretan; Maxime Annereau; Willy Kini-Matondo; Bastien Prost; Jade Prudhomme; Lina Bournane; Muriel Paul; Najet Yagoubi; Hassane Sadou-Yayé; Bernard Do;
    Publisher: MDPI AG
    Country: France

    International audience; Nirmatrelvir is an antiviral drug approved for the treatment of COVID-19. The available dosage form consists of tablets marketed under the brand name PAXLOVID®. Although knowledge of nirmatrelvir’s intrinsic stability may be useful for any potential development of other pharmaceutical forms, no data regarding this matter is available to date. Preliminary forced degradation studies have shown that the molecule is stable under oxidative and photolytic conditions, while hydrolytic conditions, both acidic and basic, have proven deleterious. Indeed, the molecule presents a priori several functions that can undergo hydrolysis, i.e., three amide moieties and a nitrile function. However, considering the degradation products formed under forced conditions and which were detected and identified by LC-UV-HRMSn, the hydrolysis process leading to their formation is selective since it involved only 2 of the 4 hydrolysable functions of the molecule. Ab initio studies based on density functional theory (DFT) have helped better understand these reactivity differences in aqueous media. Some hydrolyzable functions of nirmatrelvir differ from others in terms of electrostatic potential and Fukui functions, and this seems to correlate with the forced degradation outcomes.

  • Open Access English
    Authors: 
    Slim Fourati; Etienne Audureau; Romain Arrestier; Stéphane Marot; Claire Dubois; Guillaume Voiriot; Charles-Edouard Luyt; Tomas Urbina; Julien Mayaux; Anne-Marie Roque-Afonso; +20 more
    Publisher: HAL CCSD
    Country: France
    Project: ANR | ANTICOV (ANR-21-COVR-0022)

    Abstract Background: SARS-CoV-2 variant of concern (VOC) α spread worldwide, including in France, at the beginning of 2021. This variant was suggested to be associated with a higher risk of mortality than other variants. Little information is available in the subset of patients with severe disease admitted in the intensive care unit (ICU). We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 in order to unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes.Methods: Prospective multicentre observational cohort study. Patients aged ≥18 years admitted in 11 ICUs from Great Paris area hospitals between October 1, 2020, and May 30, 2021 (before the introduction of VOC δ (B.617.2) in France) for acute respiratory failure (SpO2≤90% and need for supplemental oxygen or ventilator support) were included. SARS-CoV-2 infection, determined by RT-PCR testing. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq).Results: 413 patients were included, 183 (44.3%) had been infected with pre-existing variants, 197 (47.7%) with variant α (B.1.1.7), and 33 (8.0%) with other variants. Patients infected with pre-existing variants were significantly older (64.9±11.9 vs 60.5±11.8 years; p=0.0005); they had significantly more frequent COPD (11.5% (n=21/183) vs 4.1% (n=8/197); p=0.009), and higher SOFA score (4 [3-8] vs 3 [2-4]; 0.0002). Day-28 mortality was not different between patients infected with pre-existing, α (B.1.1.7) or other variants (31.1% (n=57/183) vs 26.2% (n=51/197) vs 30.3% (n=10/33), respectively; p=0.550). There was no association between day-28 mortality with a specific variant or the presence of specific mutations in SARS CoV-2 genome, including 17 mutations selected in the spike protein and all 1017 non-synonymous mutations detected throughout the entire viral genome.Conclusions: At ICU admission, patients infected with pre-existing variants had a different clinical presentation from those infected with variant α (B.1.1.7) and other variants later in the course of the pandemic, but mortality did not differ between these groups. There was no association between a specific variant or SARS CoV-2 genome mutational pattern and day-28 mortality.

  • Open Access
    Authors: 
    Planchais, Cyril; Fernández, Ignacio; Bruel, Timothée; de Melo, Guilherme,; Prot, Matthieu; Beretta, Maxime; Guardado-Calvo, Pablo; Dufloo, Jérémy; Molinos-Albert, Luis,; Backovic, Marija; +122 more
    Publisher: Rockefeller University Press
    Country: France
    Project: EC | RECoVER (101003589)

    International audience; Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.

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The following results are related to COVID-19. Are you interested to view more results? Visit OpenAIRE - Explore.
252 Research products, page 1 of 26
  • Open Access
    Authors: 
    Sofía Jijón; Ahmad Al Shafie; Laura Temime; Kévin Jean; Mohamed El Kassas;
    Publisher: Cold Spring Harbor Laboratory
    Country: France

    ABSTRACTIn response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1-to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals.Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a model-based approach that accounts for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence of SARS-CoV-2 infection among HCWs. Over a total follow-up of 6,064 person-days (PD), we estimated an incidence rate (per 100 PD) of 1.05 (95% CrI: 0.58–1.65) at Hospital 1, 1.92 (95% CrI: 0.93–3.28) at Hospital 2 and 7.62 (95% CrI: 3.47–13.70) at Hospital 3. The probability for an HCW to be infected at the end of a shift was 13.7% (95% CrI: 7.8%–20.8%) and 23.8% (95% CrI: 12.2%–37.3%) for a 2-week shift at Hospital 1 and Hospital 2, respectively, which lies within the range of risk levels previously documented in standard healthcare settings, whereas it was >3-fold higher for a 7-day shift at Hospital 2 (42.6%, 95%CrI: 21.9%–64.4%). Our model-based estimates unveil a proportion of undiagnosed infections among HCWs of 46.4% (95% CrI: 18.8%–66.7%), 45.0% (95% CrI: 5.6%–70.8%) and 59.2% (95% CrI: 34.8%–78.8%), for Hospitals 1 to 3, respectively.The large variation in SARS-CoV-2 incidence we document here suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient anticipation and infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.WHAT THIS PAPER ADDSWhat is already known on this topicPrevious studies conducted in standard care settings have documented that frontline healthcare workers (HCWs) face high risk of COVID-19. Whether risk levels differ in alternative care models, such as COVID-19 quarantine hospitals in Egypt where HCWs resided in the hospital days and nights for various durations, is unknown.What this study addsCOVID-19 risk for HCWs in quarantine hospitals varies substantially between facilities, from risk levels that are in the range of those documented in standard healthcare settings to levels that were approximatively 3 times higher.How this study might affect research, practice or policyWith sufficient anticipation and infection control measures, occupational COVID-19 risk for HCWs working in quarantine hospitals can be brought down to levels similar to those observed in standard healthcare settings.

  • Open Access
    Authors: 
    Raffaele Brustia; Giuliana Amaddeo; Rami Rhaiem; Eric Levesque; Antoine Monsel; Vanessa Baaroun; Mylène Dimmock; Marc-Antoine Rousseau; Oriane Wagner-Ballon; Francoise Botterel; +2 more
    Publisher: Informa UK Limited
    Country: France

    International audience; Background: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support.Objective: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale.Design: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France.Results: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% (n = 3) and 22% (n = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively.Conclusions: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

  • Open Access English
    Authors: 
    Emmanuel Laplantine; Christine Chable-Bessia; Anne Oudin; Jitendryia Swain; Adèle Soria; Peggy Merida; Manon Gourdelier; Sarra Mestiri; Indira Besseghe; Erwan Bremaud; +11 more
    Publisher: HAL CCSD
    Country: France

    International audience; Patients with severe COVID-19 show an altered immune response that fails to control the viral spread and suffer from exacerbated inflammatory response, which eventually can lead to death. A major challenge is to develop an effective treatment for COVID-19. NF-κB is a major player in innate immunity and inflammatory process. By a high-throughput screening approach, we identified FDA-approved compounds that inhibit the NF-κB pathway and thus dampen inflammation. Among these, we show that Auranofin prevents post-translational modifications of NF-κB effectors and their recruitment into activating complexes in response to SARS-CoV-2 infection or cytokine stimulation. In addition, we demonstrate that Auranofin counteracts several steps of SARS-CoV-2 infection. First, it inhibits a raft-dependent endocytic pathway involved in SARS-CoV-2 entry into host cells; Second, Auranofin alters the ACE2 mobility at the plasma membrane. Overall, Auranofin should prevent SARS-CoV-2 infection and inflammatory damages, offering new opportunities as a repurposable drug candidate to treat COVID-19.

  • Open Access English
    Authors: 
    Charreire, Hélène; Verdot, Charlotte; Szabo de Edelenyi, Fabien; Deschasaux-Tanguy, Mélanie; Srour, Bernard; Druesne-Pecollo, Nathalie; Esseddik, Younes; Allès, Benjamin; Baudry, Julia; Deschamps, Valérie; +8 more
    Publisher: HAL CCSD
    Country: France

    International audience; Background: COVID-19 lockdowns represent natural experiments where limitations of movement impact on lifestyle behaviors. The aim of this paper was to assess how lockdowns have influenced physical activity and sedentary behaviors among French adults.Methods: 32,409 adults from the NutriNet-Santé study filled out questionnaires in April 2020 (the first 2 weeks after the start of lockdown) and in May 2020 (2 weeks before the lockdown ended). Participants were asked about changes in physical activity level and sitting time, types of physical activity performed, and main reasons for change.Results: For decreased physical activity, similar rates were found at the beginning and end of the lockdown (58 and 55%–56 and 53%, in women and men, respectively). For increased physical activity, the figures were lower (20 and 14%–23 and 18%, in women and men, respectively). The participants with a decreasing physical activity evolution were older and more likely to be living in urban areas. The main reasons for (i) decreased physical activity were limitations of movement and not liking indoor exercise, (ii) increased physical activity were to stay physically fit and healthy. Physical activity changes were inversely associated with reported depressive symptoms.Conclusions: Changes in physical activity and sedentary behaviors are heterogenous for both genders during the lockdown.

  • Open Access English
    Authors: 
    Ioana Brudasca; Quentin Lisan; Romain Tournegros; Moustafa Bensafi; Camille Ferdenzi; Arnaud Fournel; Luna Denoix; Stéphane Tringali; Maxime Fieux;
    Publisher: HAL CCSD
    Country: France

    International audience; Background: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.Methods:The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.Results: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).Conclusion: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.

  • Open Access
    Authors: 
    Timothée Bruel; Laurie Pinaud; Laura Tondeur; Delphine Planas; Isabelle Staropoli; Françoise Porrot; Florence Guivel-Benhassine; Mikaël Attia; Stéphane Pelleau; Tom Woudenberg; +12 more
    Publisher: Elsevier BV
    Country: France

    International audience; BACKGROUND: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.METHODS: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2(nd) and 3(rd) vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1.FINDINGS: Among the 38 elderly individuals recruited to the cohort study between November 23(rd), 2020 and April 29(th), 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively.INTERPRETATION: This study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity.

  • Open Access
    Authors: 
    Bastien Berger; Marc Hazzan; Nassim Kamar; Hélène Francois; Marie Matignon; Clarisse Greze; Philippe Gatault; Luc Frimat; Pierre F. Westeel; Valentin Goutaudier; +21 more
    Publisher: Elsevier BV
    Country: France

    International audience; SARS-CoV-2 pandemic evolved in two consecutive waves over 2020. Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear. In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48) and COVID-19 hospitalization period was not associated with death due to COVID in multivariate analysis (HR 0.89, 95% CI 0.67 - 1.17, p = 0.4). We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.

  • Open Access
    Authors: 
    Philippe-Henri Secretan; Maxime Annereau; Willy Kini-Matondo; Bastien Prost; Jade Prudhomme; Lina Bournane; Muriel Paul; Najet Yagoubi; Hassane Sadou-Yayé; Bernard Do;
    Publisher: MDPI AG
    Country: France

    International audience; Nirmatrelvir is an antiviral drug approved for the treatment of COVID-19. The available dosage form consists of tablets marketed under the brand name PAXLOVID®. Although knowledge of nirmatrelvir’s intrinsic stability may be useful for any potential development of other pharmaceutical forms, no data regarding this matter is available to date. Preliminary forced degradation studies have shown that the molecule is stable under oxidative and photolytic conditions, while hydrolytic conditions, both acidic and basic, have proven deleterious. Indeed, the molecule presents a priori several functions that can undergo hydrolysis, i.e., three amide moieties and a nitrile function. However, considering the degradation products formed under forced conditions and which were detected and identified by LC-UV-HRMSn, the hydrolysis process leading to their formation is selective since it involved only 2 of the 4 hydrolysable functions of the molecule. Ab initio studies based on density functional theory (DFT) have helped better understand these reactivity differences in aqueous media. Some hydrolyzable functions of nirmatrelvir differ from others in terms of electrostatic potential and Fukui functions, and this seems to correlate with the forced degradation outcomes.

  • Open Access English
    Authors: 
    Slim Fourati; Etienne Audureau; Romain Arrestier; Stéphane Marot; Claire Dubois; Guillaume Voiriot; Charles-Edouard Luyt; Tomas Urbina; Julien Mayaux; Anne-Marie Roque-Afonso; +20 more
    Publisher: HAL CCSD
    Country: France
    Project: ANR | ANTICOV (ANR-21-COVR-0022)

    Abstract Background: SARS-CoV-2 variant of concern (VOC) α spread worldwide, including in France, at the beginning of 2021. This variant was suggested to be associated with a higher risk of mortality than other variants. Little information is available in the subset of patients with severe disease admitted in the intensive care unit (ICU). We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 in order to unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes.Methods: Prospective multicentre observational cohort study. Patients aged ≥18 years admitted in 11 ICUs from Great Paris area hospitals between October 1, 2020, and May 30, 2021 (before the introduction of VOC δ (B.617.2) in France) for acute respiratory failure (SpO2≤90% and need for supplemental oxygen or ventilator support) were included. SARS-CoV-2 infection, determined by RT-PCR testing. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq).Results: 413 patients were included, 183 (44.3%) had been infected with pre-existing variants, 197 (47.7%) with variant α (B.1.1.7), and 33 (8.0%) with other variants. Patients infected with pre-existing variants were significantly older (64.9±11.9 vs 60.5±11.8 years; p=0.0005); they had significantly more frequent COPD (11.5% (n=21/183) vs 4.1% (n=8/197); p=0.009), and higher SOFA score (4 [3-8] vs 3 [2-4]; 0.0002). Day-28 mortality was not different between patients infected with pre-existing, α (B.1.1.7) or other variants (31.1% (n=57/183) vs 26.2% (n=51/197) vs 30.3% (n=10/33), respectively; p=0.550). There was no association between day-28 mortality with a specific variant or the presence of specific mutations in SARS CoV-2 genome, including 17 mutations selected in the spike protein and all 1017 non-synonymous mutations detected throughout the entire viral genome.Conclusions: At ICU admission, patients infected with pre-existing variants had a different clinical presentation from those infected with variant α (B.1.1.7) and other variants later in the course of the pandemic, but mortality did not differ between these groups. There was no association between a specific variant or SARS CoV-2 genome mutational pattern and day-28 mortality.

  • Open Access
    Authors: 
    Planchais, Cyril; Fernández, Ignacio; Bruel, Timothée; de Melo, Guilherme,; Prot, Matthieu; Beretta, Maxime; Guardado-Calvo, Pablo; Dufloo, Jérémy; Molinos-Albert, Luis,; Backovic, Marija; +122 more
    Publisher: Rockefeller University Press
    Country: France
    Project: EC | RECoVER (101003589)

    International audience; Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.