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1.
Vox Sang ; 2021 Dec 12.
Article in English | MEDLINE | ID: covidwho-1571125

ABSTRACT

Quantitation of anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) neutralizing antibodies (Nabs) is a key parameter in determining the effective dose for treatment with COVID-19 convalescent plasma (CCP). Interpretation of results from clinical trials conducted worldwide requires comparison of Nabs titres obtained from different methods. As virus neutralization tests (VNTs) are not standardized scalable or commercially available, strategies based on intensity of ELISA (Enzyme Linked Immunosorbent Assay) or chemiluminescent binding serological tests were implemented to allow comparisons and establish criteria for determining 'high-titres' of anti-SARS-CoV-2 antibodies (Abs). To this end, the FDA (Food and Drug Administration) has proposed criteria to define high-titre plasmas using different serological assays, including the one used in France for the CCP SARS-CoV-2 Abs screening (Euroimmun anti-S1 IgG). A retrospective study revealed that when using the FDA criteria (ELISA signal-to-cut-off [S/C ratio] ≥3.5), 91% of CCP had Nabs titres ≥40 as assessed with an in-house VNT. French strategy to ensure sufficient stocks of CCP of increasing titre has evolved over time. Recently, we improved our strategy by collecting only plasma from vaccinated convalescent donors as we confirmed that the mean IgG antibody level (ELISA S/C ratio) was significantly higher in plasma from vaccinated convalescent donors compared to donations from unvaccinated convalescent donors: 9.31 (CI 95%: 8.46-10.16) versus 3.22 (CI 95%: 3.05-3.39) (p < 0.001).

4.
Preprint in English | SSRN | ID: ppcovidwho-291971

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 impairs humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears to be a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2.Our study reports the effect of CCP in a cohort of patients with hematological malignancies and COVID-19 between 1 May 2020 and 1 April 2021. Overall, 112 hospitalized patients with severe COVID-19 (83 B-cell neoplasm, 19 plasma cell neoplasm, and 10 myeloid neoplasm) were included. 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 CCP transfusion. A retrospective analysis in the subgroup of COVID-19 patients with B-cell neoplasm treated with CCP (n=81) was compared to a similar group of patients (n=120) treated only with standard of care. An inverse probability of treatment weighting (IPTW) approach, performed to limit confusion and immortality bias, revealed a decreased mortality of 63% (95% CI=31%–80%) in the main analysis and 50% (95% CI=28%–66%) in the overall population of the CCP-treated group of patients with similar findings 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. Comparing CCP to other passive immunotherapy approaches such as anti-SARS-CoV-2 monoclonal antibodies is warranted.

5.
Transfusion Clinique et Biologique ; 28(4):S106-S106, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492701

ABSTRACT

Le cadre réglementaire français des recherches : la loi dite Jardé publiée en 2012 a été discutée plus de 5 ans pour entrer en vigueur en novembre 2016. Deux catégories de recherches co-existent : celles impliquant la personne humaine (RIPH) examinées par un CPP, et par opposition les « non RIPH » examinées par le HDH/CESREES/CNIL. Les RIPH sont de type 1 (interventionnelles à risque), 2 (interventionnelles à risque et contraintes minimes), ou 3 (non interventionnelles). Toute recherche qui traite des données en lien avec la personne doit aussi être en conformité avec le Règlement européen sur la protection des données (RGPD). Ainsi, de nombreuses recherches sur échantillons biologiques entrent désormais dans les RIPH3. Illustration de ce cadre réglementaire avec l'exemple de PlasmACov2, étude EFS qualifiée de RIPH3, qui a permis de constituer et de caractériser une banque de plasmas thérapeutiques de personnes guéries de la COVID-19 permettant leur évaluation dans l'essai thérapeutique de l'AP–HP, CORIPLASM qualifié de RIPH1 ;et du projet COVIDonneur, une étude de séroprévalence du SARS-CoV2 dans la population des donneurs de sang, qualifiée de RIPH3. Ce cadre français peut sembler complexe, mais il offre avec ses trois catégories de recherches et ses méthodologies de référence, une homogénéité basée sur le risque encouru par le participant. Ainsi le promoteur, responsable de la recherche doit déterminer très tôt quelle est la catégorie de sa recherche, celle-ci ayant un impact sur les démarches technico-réglementaires, sur les délais et sur les documents qui encadrent le projet tels que le protocole, l'information des personnes et le cahier de recueil des données. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

6.
Transfusion Clinique et Biologique ; 28(4):S33-S34, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492677

ABSTRACT

Lors de l'émergence de l'épidémie de SARS-CoV-2, la question d'une possible transmission par transfusion du virus a été évoquée avec la mise en évidence d'ARN dans le plasma de donneurs de sang. Une étude rétrospective a été réalisée à partir d'échantillons de biothèque transfusionnelle issus de dons de sang prélevés au pic épidémique en France (du 23 au 28 mars 2020), dans les régions les plus impactées (NORD et EST). Selon plusieurs hypothèses de prévalence, la taille d'échantillon minimale a été estimée à 6000. Le dépistage a été réalisé sur des pools de 4 échantillons (P4) par une méthode automatisée (Procleix SARS-CoV-2, Panther System, Grifols). 9672 échantillons ont été testés sous la forme de 2418 pools (P4). Cinq pools ont été dépistés positifs. Sur les 20 échantillons unitaires composant ces pools expertisés au CNR RIT (INTS), 1 seul a été confirmé par 2 méthodes différentes de RT-PCR, avec de faibles intensités réactionnelles suggérant une très faible charge virale. La mise en culture du plasma correspondant n'a pas permis d'isoler le virus. Cet échantillon provenait d'une donneuse ayant décrit rétrospectivement des symptômes évocateurs de COVID-19 dans les jours suivant son don (sans avoir été testée). Aucun EIR n'a été mis en évidence lors de l'enquête d'hémovigilance réalisée chez les receveurs du CGR et du MCP issus du don ARN SARS-CoV-2 positif. Cette étude confirme la possible présence d'ARN du virus SARS-CoV-2 dans le plasma de donneurs de sang asymptomatiques, à taux très faible, avec une prévalence d'environ 1/10 000 dons en période épidémique, sans que le caractère infectieux n'ait été démontré. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

7.
Transfusion Clinique et Biologique ; 28(4):S25-S25, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492674

ABSTRACT

L'ANSM a autorisé dans une décision du 29.04.2020, la collecte, la préparation, la conservation, la distribution et la délivrance du plasma de convalescent COVID-19 (PCC), celle-ci étant réalisée dans le cadre d'un protocole d'utilisation thérapeutique (PUT) pour les patients ayant une infection sévère à SARS-CoV-2 selon divers critères d'éligibilité. L'anonymisation de la demande est effectuée si l'indication a été validée en réunion de concertation pluridisciplinaire et que le patient a donné son consentement à la transfusion. Le nombre de demandes hebdomadaires de PCC fluctue beaucoup, avec un pic à 54 fin avril-début mai 2021. Au 13,07.2021, plus de 1000 demandes ont été reçues. Parmi les patients ayant reçu au moins un PCC, environ 2/3 sont des hommes et la quasi-totalité ont une comorbidité. Les patients sont âgés de quelques mois à 93 ans, 14 étant des enfants (6 de 0–9 ans, 8 de 10–19 ans). La distribution des groupes sanguins est similaire à celle de la population générale. À la demande de l'ANSM, un suivi avec le détail des transfusions, la survenue éventuelle d'un effet indésirable receveur ainsi que l'évolution du patient jusqu'à un bilan final est demandé et a été reçu pour une partie des patients. Certains ont bénéficié de plusieurs épisodes transfusionnels : deux pour 38 patients, et trois pour 6 patients avec une demande de suivi par séquençage viral à la recherche de sélection de variant. Les données des patients seront rétrospectivement incluses dans une cohorte nationale, dont le promoteur est l'IMEA et l'EFS un collaborateur scientifique, cohorte dans laquelle les patients recevant du PCC dans le cadre du PUT seront inclus prospectivement. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

8.
Transfusion Clinique et Biologique ; 28(4):S25-S25, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492673

ABSTRACT

Les sujets guéris (dits convalescents) ont constitué une immunité, notamment sous la forme d'anticorps spécifiques avec une activité neutralisante dans leur plasma. Ce plasma capable de transférer cette immunité de façon immédiate à un malade a été utilisé dans le passé pour le traitement de maladies infectieuses. L'EFS a mis à disposition des plasmas issus de donneurs convalescents de la COVID19 (PCC). Les donneurs guéris depuis au moins 14j donnent leur plasma par aphérèse. Le don est viro-atténué par Intercept (Cerus). Aux analyses de qualification biologique habituelles s'ajoutent la recherche des Ac anti-SARS-CoV-2, le titrage de leur pouvoir neutralisant et un dépistage du VHE. Le traitement des malades prévoit une transfusion de deux PCC puis de deux autres 24 h plus tard. Entre avril 2020 et mai 2021, 5600 plasmaphérèses ont été prélevées et préparées dans 4 à 7 régions. Selon les périodes, entre 47 et 65 % des dons étaient conformes. Ces PCC ont été transfusés à 60 patients malades de la COVID-19 dans un essai clinique national (CORIPLASM) afin d'évaluer leur efficacité. Par ailleurs, plus de 1000 patients en ont bénéficié dans le cadre compassionnel du Protocole d'Utilisation Thérapeutique. L'EFS s'est rapidement organisé pour disposer de PCC spécialement qualifiés. La transfusion de PCC semble être bénéfique chez les patients immunosupprimés, ainsi que chez les patients âgés et ceux ayant des facteurs de comorbidité pris en charge de façon très précoce. Les prélèvements se poursuivent avec des critères de sélection affinés. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

9.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1434875

ABSTRACT

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Interferon Type I/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Autoantibodies/blood , COVID-19/mortality , Case-Control Studies , Child , Child, Preschool , Critical Illness , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Infant, Newborn , Interferon-alpha/immunology , Middle Aged , Young Adult
10.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367379

ABSTRACT

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Interferon Type I/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Autoantibodies/blood , COVID-19/mortality , Case-Control Studies , Child , Child, Preschool , Critical Illness , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Infant, Newborn , Interferon-alpha/immunology , Middle Aged , Young Adult
15.
Sci Transl Med ; 12(559)2020 09 02.
Article in English | MEDLINE | ID: covidwho-724557

ABSTRACT

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Serologic Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , COVID-19 Testing , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Flow Cytometry/methods , France/epidemiology , Healthy Volunteers , Humans , Immunoprecipitation/methods , Luciferases , Male , Middle Aged , Neutralization Tests , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , SARS-CoV-2 , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology , Young Adult
16.
Antiviral Res ; 181: 104880, 2020 09.
Article in English | MEDLINE | ID: covidwho-645374

ABSTRACT

We investigated the distribution of antibodies neutralizing SARS-CoV-2 according to age, sex or blood group in French blood donors. In 464 samples collected before the emergence of SARS-CoV-2 (2017 and 2018), our virus neutralization assay had a 100% specificity. It was used to test 998 samples collected from blood donors during the last week of March or the first week of April 2020. As expected at this stage of the outbreak, the prevalence was low (2.7%) and, importantly, criteria for blood donation imply that the vast majority of seropositives had asymptomatic or pauci-symptomatic SARS-CoV-2 infections. Seroprevalence values did not differ significantly among age groups (but were slightly higher in donors <30yo and ≥60yo), and between males and females (2.82% vs 2.69%), unlike what has been observed regarding hospitalizations admission to ICU and death rates in France. By contrast, we observed that the proportion of seropositives was significantly lower in group O donors (1.32% vs 3.86% in other donors, p = 0.014). We conclude that virus infection seems to occur with a similar incidence in men and women among French blood donors, but that blood group O persons are less at risk of being infected and not only of suffering from severe clinical presentations, as previously suggested.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Blood Donors , Blood Group Antigens , COVID-19 , Coronavirus Infections/epidemiology , Female , France/epidemiology , Hospitalization , Humans , Incidence , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Risk , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies , Young Adult
17.
Vox Sang ; 115(6): 488-494, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-26729

ABSTRACT

Plasma provided by COVID-19 convalescent patients may provide therapeutic relief as the number of COVID-19 cases escalates steeply worldwide. Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. By reducing viral spread early on, such an approach may possibly downplay subsequent immunopathology. Identifying, collecting, qualifying and preparing plasma from convalescent patients with adequate SARS-CoV-2-neutralizing Ab titres in an acute crisis setting may be challenging, although well within the remit of most blood establishments. Careful clinical evaluation should allow to quickly establish whether such passive immunotherapy, administered at early phases of the disease in patients at high risk of deleterious evolution, may reduce the frequency of patient deterioration, and thereby COVID-19 mortality.


Subject(s)
Blood Specimen Collection/methods , Coronavirus Infections/blood , Pneumonia, Viral/blood , Blood Safety/methods , Blood Safety/standards , Blood Specimen Collection/standards , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunization, Passive/methods , Immunization, Passive/standards , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy
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