Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/therapy , COVID-19 Serotherapy , Plasma , Antibodies, Viral , Antibodies, Neutralizing , Neutralization TestsABSTRACT
BACKGROUND AND OBJECTIVE: The SARS-CoV-2 Omicron variant displays increased infectiveness as well as mutations resulting in reduced neutralizing activity of antibodies acquired after vaccination or infection involving earlier strains. To assess the ability of vaccinated COVID-19 convalescent plasma (CCP-V) collected before November 2021 to seroneutralize Omicron, we compared neutralizing antibody (nAb) titres of 63 samples against Omicron and earlier B.1 (D614G) strains. METHODS AND FINDINGS: Relationship between anti-Omicron titres and IgG anti-S1 levels (binding arbitrary unit: BAU/ml) was studied. Although correlated, anti-Omicron titres were significantly lower than anti-B.1 titres (median = 80 [10-1280] vs. 1280 [160-10,240], p < 0.0001). Omicron nAb titres and IgG anti-S1 levels were correlated (Spearman's rank correlation coefficient = 0.67). Anti-S1 IgG threshold at 7000 BAU/ml may allow to discard CCP-V without anti-Omicron activity (nAb titre <40). Conversely, only those with highest titres (≥160) had systematically anti-S1 IgG levels >7000 BAU/ml. CONCLUSION: A fraction of CCP-V collected before November 2021 retains anti-Omicron seroneutralizing activity that may be selected by quantitative anti-IgG assays, but such assays do not easily allow the identification of 'high-titre' CCP-V. However, collecting plasma from vaccinated donors recently infected with Omicron may be the best option to provide optimal CCP-V for immunocompromised patients infected with this variant.
Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , COVID-19 SerotherapyABSTRACT
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).
Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19/therapy , Humans , Immunization, Passive , Retrospective Studies , SARS-CoV-2 , COVID-19 SerotherapyABSTRACT
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.)
ABSTRACT
We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.