Lakshmanane Premkumar 1 , * , Bruno Segovia-Chumbez 1 , Ramesh Jadi 1 , David R. Martinez 2 , Rajendra Raut 1 , Alena Markmann 3 , Caleb Cornaby 5 , Luther Bartelt 3 , Susan Weiss 3 , Yara Park 3 , Caitlin E. Edwards 2 , Eric Weimer 4 , Erin M. Scherer 8 , Nadine Rouphael 8 , Srilatha Edupuganti 8 , Daniela Weiskopf 6 , Longping V. Tse 2 , Yixuan J. Hou 2 , David Margolis 1 , 2 , 3 , Alessandro Sette 6 , 7 , Matthew H. Collins 8 , John Schmitz 4 , Ralph S. Baric 1 , 2 , Aravinda M. de Silva 1 , *
11 June 2020
The serum level of RBD-binding antibodies correlates with SARS-CoV-2 neutralization and can be used for population-level surveillance.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.