Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies

Abstract

<b><i>Background:</i></b> Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. <b><i>Methods:</i></b> Patients who had recovered from CO­VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. <b><i>Results:</i></b> A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. <b><i>Conclusion:</i></b> We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

mRNA Vaccines Enhance Neutralizing Immunity against SARS-CoV-2 Variants in Convalescent and ChAdOx1-Primed Subjects

“…A total of 116 vaccinated individuals had no history of COVID-19; 28 were COVID-19-convalescent and analyzed separately. A total of 162 unvaccinated COVID-19-convalescent individuals served as a reference cohort [ 5 , 6 , 7 ], for which the day of positive pharyngeal swab nucleic acid amplification test (NAT) was considered as timepoint 0. Using identical platforms, we compared the different vaccination cohorts side-by-side, among one another as well as against the reference cohort (cohort I).…”

Demographic and Clinical Factors Associated with Reactivity of Anti-SARS-CoV-2 Antibodies in Serbian Convalescent Plasma Donors

“…A study in Mexico did not find a difference in the expression of anti-SARS-CoV-2 Abs between adult and children convalescents, neither between different COVID-19 severity groups [ 23 ]. Similarly, Körper et al reported no correlation of age with nAb levels in German CCP donors [ 22 ]. Bartleson et al suggested that different observations related to link between age and anti-SARS-CoV-2 Ab levels could be explained if one considers that Abs have two roles during viral infections—viral clearance and antibody-mediated enhancement of viral entry into the host cells [ 57 ].…”

“…In addition, it is previously reported that comorbidities can lead to an increased level of proinflammatory cytokines which can have a stimulatory effect on humoral response [ 63 ]. Nevertheless, Körper et al did not report the link of body weight with nAbs level in CCP donors [ 22 ]. Additionally, no correlation with anti-SARS-CoV-2 Abs level was found in the persons with chronic liver disease, chronic lung disease or diabetes [ 52 , 64 ].…”

“…Several studies have shown that anti-SARS-CoV-2 Abs levels varies according to age, gender, comorbidities, disease severity, ethnicity and blood type [ 16 , 17 , 18 , 19 , 20 , 21 ]. The link between above mentioned parameters and reactivity of anti-SARS-CoV-2 Abs could be population dependent [ 10 , 16 , 22 , 23 ]. Determining the factors associated with high levels of anti-SARS-CoV-2 Abs in populations living in specific regions (e.g., Central Balkan) could assist CCP donor selection, leading to improved treatment of COVID-19 patients.…”

Nachweis von Antikörpern gegen SARS-CoV-2

“…Detection of Anti-SARS-CoV-2 Antibodies tiierten Studien zur Anwendung von Rekonvaleszentenplasma für die Behandlung schwerer Verläufe von COVID-19 heraus. Auch der DRK-Blutspendedienst Baden-Württemberg -Hessen legte eine entsprechende Studie in Deutschland auf (CAPSID; Eudra-CT2020-001310-38, NCT04433910), für die bis Ende 2020 über 200 potenzielle Spender*innen gescreent und letztlich 319 Rekonvaleszentenplasmen von 144 Spender*innen gewonnen werden konnten [6]. Für die Testung eines Teils dieser genesenen Patient*innen wurden anfangs parallel Testplattformen verschiedener Hersteller wie Abbott, EUROIMMUN, Roche und Snibe herangezogen und mit der aufwendigen Neutralisationstestplattform des sogenannten Plaque Reduction Neutralization Test (PRNT) der Charité -Universitätsmedizin Berlin unter Verwendung von Wildtyp-SARS-CoV-2 verglichen [7,8].…”