SARS-CoV-2 antibody characterization in emergency department, hospitalized and convalescent patients by two semi-quantitative immunoassays

He S Yang,Sabrina E Racine-Brzostek,William T Lee,Danielle Hunt,Jim Yee,Zhengming Chen,Jeffrey Kubiak,Miguel Cantu,Layla Hatem,Elaine Zhong,Danielle D'Ambrosio,Amy Chadburn,Lars Westblade,Marshall Glesby,Massimo Loda,Melissa M Cushing,Zhen Zhao

doi:10.1016/j.cca.2020.06.004

Abstract

BackgroundIn the ongoing COVID-19 pandemic, there is an urgent need for comprehensive performance evaluation and clinical utility assessment of serological assays to understand the immune response to SARS-CoV-2. MethodsIgM/IgG and total antibodies against SARS-CoV-2 were measured by a cyclic enhanced fluorescence assay (CEFA) and a microsphere immunoassay (MIA), respectively. Independent performance evaluation included imprecision, reproducibility, specificity and cross-reactivity (CEFA n = 320, MIA n = 364). Clinical utility was evaluated by both methods in 87 patients at initial emergency department visit, 28 during subsequent hospitalizations (106 serial samples), and 145 convalescent patients. Totally 916 patients and 994 samples were evaluated. ResultsAgreement of CEFA and MIA was 90.4%-94.5% (Kappa: 0.81–0.89) in 302 samples. CEFA and MIA detected SARS-CoV-2 antibodies in 26.2% and 26.3%, respectively, of ED patients. Detection rates increased over time reaching 100% after 21 days post-symptom onset. Longitudinal antibody kinetic changes by CEFA and MIA measurements correlated well and exhibited three types of seroconversion. Convalescent sera showed a wide range of antibody levels. ConclusionRigorously validated CEFA and MIA assays are reliable for detecting antibodies to SARS-CoV-2 and show promising clinical utility when evaluating immune response in hospitalized and convalescent patients, but are not useful for early screening at patient’s initial ED visit.

Highlights

The ongoing global pandemic of Coronavirus Disease-2019 (COVID19) has rapidly spread with globally over 3.7 million confirmed cases and over 259,000 total deaths as of May 5, 2020 [1]
Acute symptoms and signs of SARS-CoV-2 infection are highly nonspecific and include fever, cough, fatigue, myalgia, and dyspnea with some patients progressing to Abbreviations: COVID-19, corona virus disease-2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ED, emergency department; EUA, Emergency Use Authorization; CEFA, cyclic enhanced fluorescence assay; MIA, microsphere immunoassay; RT-PCR, real-time reverse transcription polymerase chain reaction; SARS-CoV, severe acute respiratory syndrome coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; ICU, intensive care unit
The demographics did not vary significantly between the COVID-19 positive and negative patients in terms of age, race/ethnicity or major comorbidities. Of those patients admitted to the hospital, none of the COVID-19 negative patients required ICU care or intubation

Summary

Introduction

The ongoing global pandemic of Coronavirus Disease-2019 (COVID19) has rapidly spread with globally over 3.7 million confirmed cases and over 259,000 total deaths as of May 5, 2020 [1]. Some other individuals are asymptomatic carriers [5,6,7] These characteristics of the disease create an urgent need to develop serological tests to identify asymptomatic silent infections, evaluate patient immune response, better predict disease progression and improve our understanding of the epidemiology, including transmission patterns, of SARS-CoV-2. In the ongoing COVID-19 pandemic, there is an urgent need for comprehensive performance evaluation and clinical utility assessment of serological assays to understand the immune response to SARS-CoV2. Conclusion: Rigorously validated CEFA and MIA assays are reliable for detecting antibodies to SARS-CoV-2 and show promising clinical utility when evaluating immune response in hospitalized and convalescent patients, but are not useful for early screening at patient’s initial ED visit

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