SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood

Dianna L Ng,Li Du,Sandra Pearce,Phillip Williamson,Andrew G Levine,Edward C Thornborrow ,Gregory M Goldgof,Mary A Rodgers ,Andrea Granados,Valerie Green,Chuanyi M Lu,Jill Hakim ,John Prostko,Joanna Balcerek,Kelly E Coller ,Daniel Qazi,Ching Ying Oon ,Nancy K Hills,Susan L Stramer,Lucy Han ,Neil M Neumann,Elaine Hsu,Kevin Reyes,Yale A Santos,Brian Custer,Sagar P Bapat,Mars Stone,Dustin R Glasner,John Hackett,Lori Pham,Fariba Alazzeh,David N Nguyen,Venice Servellita,Candace Wang,Kent Truong,Brian R Shy,Michael P Busch,Wei Gu,Sergej Franz,Steve Miller,Jeffrey D Whitman,Theodore W Kurtz ,Alicia Sotomayor-González ,Naomi Akagi,Satish K Pillai,Kirk Sujishi,Graham Simmons,Claudia Sánchez San Martín ,Charles Y Chiu

doi:10.1038/s41467-020-18468-8

Abstract

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.

Highlights

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV2-specific antibodies in different populations has remained unclear
These studies demonstrate that SARS-CoV-2 seroprevalence in the San Francisco Bay Area was very low, suggesting limited circulation of the virus in the community as of early March, and that IgG and IgM titers are predictive of neutralizing activity, with high positive percent agreement
Prior to assessing seroprevalence of SARS-CoV-2 antibodies in San Francisco Bay area populations, we verified the performance of the Abbott Architect SARS-CoV-2 IgG (FDA Emergency Use Authorization (EUA)) and IgM assays

Summary

Introduction

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV2-specific antibodies in different populations has remained unclear. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93% These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity. We investigate the longitudinal dynamics of IgG, IgM, and in vitro neutralizing antibody titers in hospitalized COVID-19 patients over time These studies demonstrate that SARS-CoV-2 seroprevalence in the San Francisco Bay Area was very low, suggesting limited circulation of the virus in the community as of early March, and that IgG and IgM titers are predictive of neutralizing activity, with high positive percent agreement

Methods

Results

Conclusion