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1.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.09.22278329

ABSTRACT

Background: Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. Early transfusion of high antibody titre CCP may be beneficial, especially in case of underlying immunosuppression. Methods: The CORIPLASM study was a multicentric, open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19 pneumonia, including patients with underlying immunosuppression. Patients hospitalised with COVID-19 for less than 9 days were assigned to receive 2 plasma units/day over 2 days (CCP) or usual care (UC) alone. Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) >= 6 on the 10-point scale on day 4 and survival without ventilation or additional immunomodulatory treatment by day 14. Main analysis was conducted on the whole population and a planned subgroup analysis was performed according to immunosuppression status. Findings: A total of 120 patients were recruited between April 16, 2020, and April 21, 2021, and assigned to CCP (n=60) or UC (n=60) with a 28 day-follow-up. The median time from symptoms onset to randomisation (days) was 7.0 [interquartile range (IQR) 5.0-9.0] and 7.0 [IQR 4.0-8.5] in CCP and UC, respectively. Thirteen (22%) patients with CCP had a WHO-CPS >= 6 at day 4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95% confidence interval (CI), 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0.10 -1.53]), and 7 (12%) with CCP and 12 (20%) with UC at day 28 (aHR 0.51 [95% CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in patients with underlying immunosuppression (HR 0.37 [95% CI 0.14-0.97]). Serious adverse events were noted in 30 (50%) and 26 (43%) patients with CCP or UC, respectively. Interpretation: CCP treatment did not improve early outcomes in patients with mild-to-moderate form COVID-19 pneumonia but was associated with reduced mortality in the subgroup of immunosuppressed patients. Trial registration: clinicaltrials.gov Identifier: NCT04345991


Subject(s)
Pneumonia , Death , Immunologic Deficiency Syndromes , COVID-19
2.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.07.29.22278190

ABSTRACT

SUMMARY We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that ∼15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.

4.
Jeremy Manry; Paul Bastard; Adrian Gervais; Tom Le Voyer; Jérémie Rosain; Quentin Philippot; Eleftherios Michailidis; Hans-Heinrich Hoffmann; Shohei Eto; Marina Garcia-Prat; Lucy Bizien; Alba Parra-Martínez; Rui Yang; Liis Haljasmägi; Mélanie Migaud; Karita Särekannu; Julia Maslovskaja; Nicolas de Prost; Yacine Tandjaoui-Lambiotte; Charles-Edouard Luyt; Blanca Amador-Borrero; Alexandre Gaudet; Julien Poissy; Pascal Morel; Pascale Richard; Fabrice Cognasse; Jesus Troya; Sophie Trouillet-Assant; Alexandre Belot; Kahina Saker; Pierre Garçon; Jacques Rivière; Jean-Christophe Lagier; Stéphanie Gentile; Lindsey Rosen; Elana Shaw; Tomohiro Morio; Junko Tanaka; David Dalmau; Pierre-Louis Tharaux; Damien Sene; Alain Stepanian; Bruno Mégarbane; Vasiliki Triantafyllia; Arnaud Fekkar; James Heath; Jose Franco; Juan-Manuel Anaya; Jordi Solé-Violán; Luisa Imberti; Andrea Biondi; Paolo Bonfanti; Riccardo Castagnoli; Ottavia Delmonte; Yu Zhang; Andrew Snow; Steve Holland; Catherine Biggs; Marcela Moncada-Vélez; Andrés Arias; Lazaro Lorenzo; Soraya Boucherit; Dany Anglicheau; Anna Planas; Filomeen Haerynck; Sotirija Duvlis; Robert Nussbaum; Tayfun Ozcelik; Sevgi Keles; Aziz Bousfiha; Jalila El Bakkouri; Carolina Ramirez-Santana; Stéphane Paul; Qiang Pan-Hammarstrom; Lennart Hammarstrom; Annabelle Dupont; Alina Kurolap; Christine Metz; Alessandro Aiuti; Giorgio Casari; Vito Lampasona; Fabio Ciceri; Lucila Barreiros; Elena Dominguez-Garrido; Mateus Vidigal; Mayana Zatz; Diederik van de Beek; Sabina Sahanic; Ivan Tancevski; Yurii Stepanovskyy; Oksana Boyarchuk; Yoko Nukui; Miyuki Tsumura; Loreto Vidaur; Stuart Tangye; Sonia Burrel; Darragh Duffy; Lluis Quintana-Murci; Adam Klocperk; Nelli Kann; Anna Shcherbina; Yu-Lung Lau; Daniel Leung; Matthieu Coulongeat; Julien Marlet; Rutger Koning; Luis Reyes; Angélique Chauvineau-Grenier; Fabienne Venet; guillaume monneret; Michel Nussenzweig; Romain Arrestier; Idris Boudhabhay; Hagit Baris-Feldman; David Hagin; Joost Wauters; Isabelle Meyts; Adam Dyer; Sean Kennelly; Nollaig Bourke; Rabih Halwani; Fatemeh Sharif-Askari; Karim Dorgham; Jérôme Sallette; Souad Mehlal-Sedkaoui; Suzan AlKhater; Raúl Rigo-Bonnin; Francisco Morandeira; Lucie Roussel; Donald Vinh; Christian Erikstrup; Antonio Condino-Neto; Carolina Prando; Anastasiia Bondarenko; András Spaan; Laurent Gilardin; Jacques Fellay; Stanislas Lyonnet; Kaya Bilguvar; Richard Lifton; Shrikant Mane; Mark Anderson; Bertrand Boisson; Vivien Béziat; Shen-Ying Zhang; Evangelos Andreakos; Olivier Hermine; Aurora Pujol; Pärt Peterson; Trine Hyrup Mogensen; Lee Rowen; James Mond; Stéphanie Debette; Xavier deLamballerie; Charles Burdet; Lila Bouadma; Marie Zins; Pere Soler-Palacin; Roger Colobran; Guy Gorochov; Xavier Solanich; Sophie Susen; Javier Martinez-Picado; Didier Raoult; Marc Vasse; Peter Gregersen; Carlos Rodríguez-Gallego; Lorenzo Piemonti; Luigi Notarangelo; Helen Su; Kai Kisand; Satoshi Okada; Anne Puel; Emmanuelle Jouanguy; Charles Rice; Pierre Tiberghien; Qian Zhang; Jean-Laurent Casanova; Laurent Abel; Aurélie Cobat.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1225906.v1

ABSTRACT

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.


Subject(s)
COVID-19
5.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.29.21268525

ABSTRACT

Patients with hematological malignancies and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatment impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancies and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n=81) or not (n=120) with CCP between 1 May 2020 and 1 April 2021. The overall survival of the whole cohort was 65% [56-74.9] and 77.5% [68.5-87.7] for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibodies therapy was associated with better overall survival whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI=31%-80%) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.


Subject(s)
Lymphoma, B-Cell , COVID-19 , Hematologic Neoplasms
6.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.04.21.20068858

ABSTRACT

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre- epidemic individuals, 51 patients from Hopital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C- terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV- 2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.


Subject(s)
COVID-19
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