Anti-SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

Evangelos Terpos; Marianna Politou; Theodoros N Sergentanis; Andreas Mentis; Margherita Rosati; Dimitris Stellas; Jenifer Bear; Xintao Hu; Barbara K Felber; Vassiliki Pappa; Maria Pagoni; Elisavet Grouzi; Stavroula Labropoulou; Ioanna Charitaki; Ioannis Ntanasis-Stathopoulos; Dimitra Moschandreou; Anthi Bouhla; Stylianos Saridakis; Eleni Korompoki; Chara Giatra; Tina Bagratuni; Angelos Pefanis; Sotirios Papageorgiou; Alexandros Spyridonidis; Anastasia Antoniadou; Anastasia Kotanidou; Konstantinos Syrigos; Konstantinos Stamoulis; George Panayiotakopoulos; Sotirios Tsiodras; Leonidas Alexopoulos; Meletios A Dimopoulos; George N Pavlakis

doi:10.3390/microorganisms8121885

Anti-SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

Microorganisms. 2020 Nov 28;8(12):1885. doi: 10.3390/microorganisms8121885.

Authors

Evangelos Terpos¹, Marianna Politou², Theodoros N Sergentanis¹, Andreas Mentis³, Margherita Rosati⁴, Dimitris Stellas^{4

5}, Jenifer Bear⁶, Xintao Hu⁶, Barbara K Felber⁶, Vassiliki Pappa⁷, Maria Pagoni⁸, Elisavet Grouzi⁹, Stavroula Labropoulou³, Ioanna Charitaki¹, Ioannis Ntanasis-Stathopoulos¹, Dimitra Moschandreou⁹, Anthi Bouhla⁷, Stylianos Saridakis¹⁰, Eleni Korompoki¹, Chara Giatra⁸, Tina Bagratuni¹, Angelos Pefanis¹¹, Sotirios Papageorgiou⁷, Alexandros Spyridonidis¹², Anastasia Antoniadou¹³, Anastasia Kotanidou¹⁴, Konstantinos Syrigos¹⁵, Konstantinos Stamoulis¹⁶, George Panayiotakopoulos^{17

18}, Sotirios Tsiodras^{13

18}, Leonidas Alexopoulos¹⁹, Meletios A Dimopoulos¹, George N Pavlakis⁴

Affiliations

¹ Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
² Hematology Laboratory Blood Bank, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
³ Public Health Laboratories, Hellenic Pasteur Institute, 11521 Athens, Greece.
⁴ Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
⁵ Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., 11635 Athens, Greece.
⁶ Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
⁷ Hematology Unit, Second Department of Internal Medicine, Attikon University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
⁸ BMT Unit, Department of Hematology and Lymphomas, Evangelismos General Hospital, 10676 Athens, Greece.
⁹ Department of Transfusion Service and Clinical Hemostasis, "Saint Savvas" Oncology Hospital, 11522 Athens, Greece.
¹⁰ Blood Bank, Evangelismos General Hospital, 10442 Athens, Greece.
¹¹ Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, 11527 Athens, Greece.
¹² BMT Unit, University Hospital of Patras, School of Medicine, University of Patras, 26500 Patras, Greece.
¹³ Fourth Department of Internal Medicine, Attikon University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
¹⁴ First Department of Critical Care Medicine and Pulmonary Services, Evangelismos General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
¹⁵ Oncology Unit, Third Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
¹⁶ Hellenic National Blood Transfusion Center, 13678 Athens, Greece.
¹⁷ Pharmacology Laboratory, School of Medicine, University of Patras, 26500 Patras, Greece.
¹⁸ National Public Health Organization, 15123 Athens, Greece.
¹⁹ Biomedical Systems Laboratory, National Technical University of Athens, 11527 Athens, Greece.

Abstract

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14-104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

Keywords: Covid-19; SARS-CoV-2; antibodies; convalescent plasma; novel coronavirus.