Development of a SARS-CoV-2 Total Antibody Assay and the Dynamics of Antibody Response over Time in Hospitalized and Nonhospitalized Patients with COVID-19
Authors: Vogelzang Erik H. , Loeff Floris C. , Derksen Ninotska I. L. , Kruithof Simone , Ooijevaar-de Heer Pleuni , van Mierlo Gerard , Linty Federica , Mok Juk Yee , van Esch Wim , de Bruin Sanne , Vlaar Alexander P. J. ,   Amsterdam University Medical Center COVID-19 Biobank Study Group, Hemke Robert , van de Beek Diederik , Beudel Martijn , Brouwer Matthijs C. , Geerts Bart , Hollmann Markus , Preckel Bennedikt , Veelo Denise , Zwinderman A. H. (Koos) , Geijtenbeek Theo , Hafkamp Florianne , Bax Diane , Cloherty Alex , van Agtmael Michiel , Bomers Marije , Geerlings Suzanne , Grobusch Martin P. , Harris Vanessa , Hermans Sabine M. , Hovius Joppe W. , Nellen Jeaninne , Peters Edgar , van der Poll Tom , Prins Jan M. , Sigaloff Kim , Stijnis Cornelis S. , van der Valk Marc , van Vugt Michèle , Wiersinga W. Joost , Bree Godelieve , Vlaar Alexander P. J. , de Bruin Sanne , Algera Anne Geke , van Baarle Frank , Bos Lieuwe , Botta Michela , Bulle Esther , Elbers Paul , Fleuren Lucas , Girbes Armand , Hagens Laura , Heunks Leo , Horn Janneke , van Mourik Mourik , Paulus Frederique , Raasveld Jorinde , Schultz Marcus , Smit Marry , Stilma Willemke , Thoral Patrick , Tsonas Anissa , de Vries Heder , Schuurmans Alex , de Jong Menno , Bugiani Marianna , Bogaard Harm Jan , Teunissen Charlotte , Hamann Jorg , Seppen Bart , Leeuw Maureen , van Oudheusden Anne J. G. , Buiting Anton G. M. , Jim Kin Ki , Vrielink Hans , Swaneveld Francis , Vidarsson Gestur , van der Schoot C. Ellen , Wever Peter C. , Li Wentao , van Kuppeveld Frank , Murk Jean-Luc , Bosch Berend Jan , Wolbink Gerrit-Jan , Rispens Theo 
Published: October 2020

Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections often cause only mild disease that may evoke relatively low Ab titers compared with patients admitted to hospitals. Generally, total Ab bridging assays combine good sensitivity with high specificity. Therefore, we developed sensitive total Ab bridging assays for detection of SARS-CoV-2 Abs to the receptor-binding domain (RBD) and nucleocapsid protein in addition to conventional isotype-specific assays. Ab kinetics was assessed in PCR-confirmed, hospitalized coronavirus disease 2019 (COVID-19) patients (n = 41) and three populations of patients with COVID-19 symptoms not requiring hospital admission: PCR-confirmed convalescent plasmapheresis donors (n = 182), PCR-confirmed hospital care workers (n = 47), and a group of longitudinally sampled symptomatic individuals highly suspect of COVID-19 (n = 14). In nonhospitalized patients, the Ab response to RBD is weaker but follows similar kinetics, as has been observed in hospitalized patients. Across populations, the RBD bridging assay identified most patients correctly as seropositive. In 11/14 of the COVID-19–suspect cases, seroconversion in the RBD bridging assay could be demonstrated before day 12; nucleocapsid protein Abs emerged less consistently. Furthermore, we demonstrated the feasibility of finger-prick sampling for Ab detection against SARS-CoV-2 using these assays. In conclusion, the developed bridging assays reliably detect SARS-CoV-2 Abs in hospitalized and nonhospitalized patients and are therefore well suited to conduct seroprevalence studies.