Clinical Validation and Performance Evaluation of the Automated Vitros Total Anti–SARS-CoV-2 Antibodies Assay for Screening of Serostatus in COVID-19

Emily Garnett, PhD; Joanna Jung, PhD; Estella Tam, BS; Deepthi Rajapakshe, MS; Stephen Cheney, MD; Cameron Brown, PhD; Jing Cao, PhD; Kenneth Muldrew, MD; Ila Singh, MD, PhD; James Versalovic, MD, PhD; Sridevi Devaraj, PhD, DABCC, FRSC

Disclosures

Am J Clin Pathol. 2020;154(6):742-747. 

In This Article

Abstract and Introduction

Abstract

Objectives: Evaluation of serostatus against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as an important tool in identification of exposure to coronavirus disease 2019 (COVID-19). We report on the validation of the Vitros Anti–SARS-CoV-2 Total (CoV2T) assay for qualitative serologic testing of SARS-CoV-2 antibodies.

Methods: We performed validation studies according to Commission of Office Laboratories Accreditation guidelines, using samples previously tested for SARS-CoV-2 by reverse transcription–polymerase chain reaction (RT-PCR). We evaluated precision, analytical interferences, and cross-reactivity with other viral infections; evaluated concordance with molecular and other serologic testing; and evaluated seroconversion.

Results: The Vitros CoV2T assay exhibited acceptable precision and did not exhibit cross-reactivity with other acute respiratory virus infections. The CoV2T assay exhibited 100% negative predictive agreement (56/56) and 71% positive predictive agreement (56/79) with RT-PCR across all patient samples and was concordant with other serologic assays. Concordance with RT-PCR was 97% more than 7 days after symptom onset. The CoV2T assay was robust to icterus and lipemia but had interference from significant hemolysis.

Conclusions: The Vitros CoV2T assay was successfully validated in our laboratory. We anticipate it will be a useful tool in screening for exposure to SARS-CoV-2; however, the use of the CoV2T and other serologic assays in the clinical management of patients with COVID-19 is unknown and must be evaluated in future studies.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus identified in China in late 2019.[1] The resultant disease, coronavirus disease 2019 (COVID-19), has a variety of presentations from mild disease to severe pneumonia requiring mechanical ventilatory support, as well as thrombotic strokes, multi-inflammatory syndrome, and others.[2] COVID-19 has become a global pandemic and continues to spread, producing substantial morbidity, mortality, and economic impact.[3] Accurate epidemiologic information is important for the development of effective public health measures for containment and mitigation of COVID-19; however, case identification has been complicated by the wide range of clinical presentations of COVID-19. The mainstay of diagnostic testing for COVID-19, as with most respiratory viral infections, is molecular detection of SARS-CoV-2 viral RNA in respiratory swab specimens. Molecular diagnostic testing is preferred given its high specificity and the ability to yield a rapid diagnosis during acute infection, but preanalytical challenges (eg, nasopharyngeal swab sampling) and analytical challenges have limited the utility of molecular testing as a means to screen for exposure to SARS-CoV-2.[4,5] The abundance of detectable nucleic acid also decreases over time; other studies have suggested the RNA-positive rate may decline to under 30% by 3 weeks after symptom onset.[6] Consequently, the extent of COVID-19 infection remains unknown in many populations, limiting the ability to assess case fatality rates and hampering efforts to effectively quarantine infected individuals and limit spread.

Serologic testing is used for the identification and management of many infectious diseases to provide evidence that a person has had exposure to a pathogen and mounted an immune response. The laboratory workflow for serologic testing is typically simpler, faster, and less expensive than that of molecular testing, and specimen collection is more reproducible, which offers advantages for widespread screening. Serologic testing has been suggested as a means of surveillance to determine actual numbers of COVID-19 infections, which can subsequently inform public health strategies. Previous studies have indicated that seropositivity in COVID-19 begins to occur approximately 7 days after symptom onset, although how long seropositivity remains after recovery and to what extent it indicates immunity to reinfection are not yet established.[7]

Recommendations from the Centers for Disease Control and Prevention and the US Food and Drug Administration (FDA) indicate the use of total (IgG and IgM) anti–SARS-CoV-2 antibodies as evidence of previous viral exposure.[8] Only a few serologic assays have been granted emergency use authorization (EUA) by the FDA for this purpose, but limited data are available on the analytical or clinical performance of these tests. In this study, we describe validation of one of the first assays to receive EUA on an automated platform, the Vitros Anti–SARS-CoV-2 Total (CoV2T; Ortho Clinical Diagnostics) antibody assay, for screening of previous exposure to SARS-CoV-2 in our patient population.

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