Lab Matters Fall 2020 - Page 20

INDUSTRY MATTERS

Clinical Use of Serologic Methods in the COVID-19 Pandemic

By Scott Hauenstein , PhD , senior manager , Scientific Affairs , Bio-Rad Laboratories
SARS-CoV-2 was first identified in December 2019 and has since rapidly spread around the globe with greater than 55.2 million cases and 1.3 million deaths . 1 Current strategies for diagnosis rely on nucleic acid amplification tests ( NAAT ) which detect viral RNA in respiratory specimens from individuals with symptoms of COVID-19 . In comparison to NAAT , antibody-based assays measure the host ’ s humoral immune response to current or past infection and may play an important role in understanding the epidemiology of SARS-CoV-2 . 2
For example , a serologic study by the US Centers for Disease Control and Prevention ( CDC ) estimated that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases by NAAT . 3 Antibodies typically become detectable 1-3 weeks after symptom onset . Antibody increase correlates with a decrease in respiratory track viral load , leading to reduced infectiousness and possibly some shortterm immunity . However , based on the available evidence at this time , serologic tests should not be used to determine immunity or risk of re-infection and it is recommended that more data is needed before modifying public health recommendations based on serologic test results . 4
Choices , Choices
Serologic assays have been developed for IgG , IgM and IgG , or total antibody ( IgA , IgM , IgG ) with widely variable performance . The US Food and Drug Administration ( FDA ) recommends that laboratories utilize validated tests with Emergency Use Authorizations ( EUAs ) due to the poor performance of many tests that were initially introduced on the market . 5 There are currently more than 50 EUA serology tests available that detect different antigens including the spike protein and its receptor binding domain as well as the nucleocapsid . Recent Infectious Disease Society of America ( IDSA ) guidelines indicate the usage of antibody tests for two scenarios in addition to use in epidemiologic studies . 6
First , it may be helpful when an individual has high clinical suspicion of COVID-19 and the results of repeat NAAT are
The BioPlex 2200 System : a fully automated , random access multiplex testing platform negative or have not been performed . In this case a total Ab or IgG assay should be performed 3-4 weeks after the onset of symptoms . Second , detection of anti-SARS-CoV-2 antibodies is useful for assessments of suspected multisystem inflammatory syndrome in children . It is important to minimize false positive test results by choosing an assay with high specificity (> 99 %) and by testing populations and individuals with an elevated likelihood of previous exposure to SARS-CoV-2 . 4 An orthogonal testing algorithm ( such as employing tests with different targets in sequence when the first test yields a positive result ) can be used when the expected PPV of a single test is low . 4
When to Use
A recent Cochrane review attempted to evaluate COVID-19 serologic test performance by analyzing 54 studies that included 15,976 samples . 7 The serologic tests included both rapid and laboratory-based methods such as ELISA for detection of IgG , IgM , or IgG / IgM antibodies . Test sensitivity was strongly related to time since onset of symptoms , with sensitivity for IgG / IgM tests exceeding 90 % between 15 and 35 days and laboratory-based methods appearing to outperform rapid point-of-care tests . Specificity was high (> 98 %) for all types of antibody .
The Platelia SARS-CoV-2 Total Ab is an example of a test with high specificity ( 99.3 %) and sensitivity ( 98 %) that may be utilized as recommended by these guidelines . 8 A recent publication in JCM highlighted an early evaluation of the assay comparing its performance in clinical samples to five other commercial antibody tests . 9 The study demonstrated > 91 % sensitivity when utilized after 14 days and 100 % after 21 days and “ found Abbott , Affinity , and Bio-Rad to have the highest clinical sensitivity and specificity compared to the other EIAs .” In addition , the BioPlex 2200 SARS-CoV-2 IgG Panel ( pending EUA ) may be used for
18 LAB MATTERS Fall 2020
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