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2648 Rapid Reduction of Anti–Sars-Cov-2 Antibodies in Convalescent Plasma Donors; Results of a Phase 2 Clinical Study

Program: Oral and Poster Abstracts
Session: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III
Hematology Disease Topics & Pathways:
Coronaviruses, Adult, SARS-CoV-2/COVID-19, Technology and Procedures, Study Population, Clinically relevant, serologic tests
Monday, December 7, 2020, 7:00 AM-3:30 PM

Evangelos Terpos, MD, PhD1, Marianna Politou, MD2*, Theodoros N Sergentanis, MD, PhD1*, Andreas Mentis, MD3*, Vassiliki Pappa, MD4*, Maria Pagoni, MD5*, Elisavet Grouzi, MD6*, Stavroula Labropoulou, PhD3*, Ioanna Charitaki1*, Dimitra Moschandreou, MD6*, Anthi Bouhla, MD4*, Stylianos Saridakis, MD7*, Eleni Korompoki, MD1*, Chara Giatra, MD5*, Tina Bagratuni, PhD1*, Angelos Pefanis, MD8*, Sotirios Papageorgiou, MD, PhD4*, Alexandros Spyridonidis, MD, PhD9*, Anastasia Antoniadou, MD, PhD10*, Anastasia Kotanidou, MD11*, Konstantinos Syrigos, MD, PhD12*, Konstantinos Stamoulis, MD13*, George Panayiotakopoulos, MD, PhD14,15*, Sotirios Tsiodras, MD, PhD10,15*, Leonidas Alexopoulos, PhD16* and Meletios A Dimopoulos17

1Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
2Hematology Laboratory Blood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
3Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece
4Second Department of Internal Medicine, Hematology Unit, Attikon University General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
5Department of Hematology and Lymphomas, BMT Unit, Evangelismos General Hospital, Athens, Greece
6Department of Transfusion Service and Clinical Hemostasis, “Saint Savvas” Oncology Hospital, Athens, Greece
7Blood Bank, Evangelismos General Hospital, Athens, Greece
8Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece
9BMT Unit, University Hospital of Patras, University of Patras, School of Medicine, Patras, Greece
10Fourth Department of Internal Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
11First Department of Critical Care Medicine and Pulmonary Services, Evangelismos General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
12Third Department of Medicine, Oncology Unit, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
13Hellenic National Blood Transfusion Center, Athens, Greece
14Pharmacology Laboratory, University of Patras, School of Medicine, Patras, Greece
15National Public Health Organization, Athens, Greece
16Biomedical Systems Laboratory, National Technical University of Athens, Athens, Greece
17Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece

Introduction: Convalescent plasma is a promising therapeutic option for corona virus disease 2019 (COVID-19). A recent study in 34 COVID-19 patients showed a reduction of recovered patients antibodies within 3 months of infection. The aim on this analysis was to evaluate the antibody titers and explore possible correlations with disease characteristics in volunteer donors, who participated in a phase 2 study for the use of convalescent plasma for the treatment of severe COVID-19 infection.

Patients and Methods: This in an ongoing phase 2 study (NCT04408209) for the use of convalescent plasma for severe COVID-19. This analysis reports the results of the first part of the study, regarding the presence of anti-SARS-CoV-2 antibodies in volunteer plasma donors and their correlation with disease characteristics. The main Inclusion criteria for plasma donors included: (i) confirmed SARS-CoV-2 infection by PCR of the nasal/pharyngeal swab; (ii) interval of at least 14 days after complete recovery from COVID-19; (iii) presence of anti-SARS-CoV-2 antibodies; (iv) two negative SARS-CoV-2 PCR results (the second at least 7 days prior to plasmapheresis). For the detection of anti-SARS-CoV-2 antibodies we used two commercially developed assays: one ELISA assay (Euroimmun Medizinische Labordiagnostika AG, Lubeck, Germany), which detects antibodies against the recombinant Spike protein of the virus (S1 domain) and a multiplex assay (ProtATonce Ltd, Athens, Greece) based on the Luminex® xMAP™ technology that detects total antibodies (IgG/IgM/IgA) and individual antibody isotypes IgG, IgM and IgA against 3 SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD).

Results: To-date, 260 (137M/123F) possible plasma donors were tested for the presence of anti-SARS-CoV-2 antibodies. At the time of their COVID-19 diagnosis, 20 (7.7%) were asymptomatic, 157 (60.3%) were symptomatic but did not need hospitalization and 83 (32%) were hospitalized. Median time from the day of their first symptom or PCR+ (for asymptomatic patients) till the day of screening was 62 (range: 14-104) days. Anti-SARS-CoV-2 antibodies were detected in 229 (88%) donors with the Euroimmun assay and in 238 (91.5%) with the multiplex assay (including the 229 who had antibodies with the Euroimmun method). Univariate analysis showed that donors who had asymptomatic COVID-19 had lower antibody titer compared to those who had symptomatic disease but did not need hospitalization or those who hospitalized (Fig. A-D). Donors <50 years had lower antibody titer compared with older patients [for Euroimmun method, median (IQR): 3.94 (5.10) vs. 7.34 (6.16); p<0.0001], while patients who were tested within 60 days from the first day of symptom or PCR+ (for asymptomatic patients) had higher antibody titer [6.09 (6.52) vs. 4.68 (6.12); p=0.024]. The multivariate analysis showed that age ≥50 years (OR 2.88, 95% CI:1.60-5.18; p<0.001) and need for hospitalization (OR 4.11, 95% CI:2.13-7.90; p<0.001) correlated with higher antibody titers, while asymptomatic phase (OR 0.10, 95% CI:0,01-0.82; p<0.001) and testing within ≥60 days post symptoms onset (OR 0.36, 95% CI:0.20-0.66; p=0.001) correlated with lower antibody titers. In the multivariate logistic regression analysis examining associations between individual symptoms and antibody levels, there was strong correlation between anti-SARS-CoV-2 antibodies and anosmia (OR 11.14, 95% CI:3.92-31.67; p<0.001), loss of taste (OR 5.50, 95% CI:2.23-13.56; p<0.001), fever (OR 4.25, 95% CI:1.90-9.51; p<0.001), and headache (OR 2.34, 95% CI:1.09-5.03; p=0.029). To-date, plasmapheresis was performed in 74 patients with anti-SARS-CoV-2 antibodies, within a median time of 12 (8-19) days after screening; the respective median time (range) from the first day of symptoms or PCR+ was 52 (14-84) days. Interestingly, there was a significant reduction in the antibody titers between the day of screening and the day of plasmapheresis [Fig. E].

Conclusion: Lower anti-SARS-CoV-2 antibody titers, against all studied epitopes, are found in asymptomatic patients, in patients <50 years and in those who were tested ≥60 days post onset of first symptoms. The rapid reduction of anti-SARS-CoV-2 antibodies in our cohort reveals a time pattern of reduction, although we do not know if neutralizing antibodies share the same trend or if this reduction affects the host immunity against SARS-CoV-2.

Disclosures: Terpos: Amgen: Honoraria, Research Funding; BMS: Honoraria; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Other: travel expenses , Research Funding; Celgene: Honoraria; Sanofi: Honoraria. Pappa: Genesis pharma SA: Research Funding. Dimopoulos: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau.

*signifies non-member of ASH