CONTINUING EDUCATION :: ANTIBODIES


are tests that detect individual antibody isotypes (IgG or IgM, or IgA) and tests that detect a combination of total antibody either IgG/IgM or IgG/IgM/IgA, where no differentiation of the specific isotype is made.20


IgM tests typically have lower


sensitivity to detect past infection com- pared to IgG or total antibody (Figure 3).20 Tests designed to detect and differenti-


ate between IgM and IgG in combination and IgA typically have lower specificity than IgG or total antibody.20


Combined


IgG/IgM assays are more sensitive than assays that measure either antibody sepa- rately.9


To have substantial clinical utility, a


serology test must be both highly sensitive and specific.20 Total antibody or IgG tests are pre- ferred due to increased sensitivity (Figure 3) and specificity, compared to IgG/IgM, IgM, or IgA tests.20


Compared to other


antibody classes, detection of IgG or total antibody at 3-4 weeks post symptom onset provides highest sensitivity and specific- ity, leading to lower false negative and false positive result rates.20


Total antibody


tests that include IgA may have increased clinical utility, since at least one study has shown that a subset of SARS-CoV-2 infected individuals seroconverted with only an IgA response.6 The FDA has set minimal performance standards for SARS-CoV-2 Ab assays using PCR as the comparator. For tests that detect and differentiate IgM and IgG antibodies, clinical agreement studies should demonstrate an overall combined positive percent agreement (PPA) and negative percent agreement (NPA) of at least 90% and 95% respectively, and IgM PPA of at least 70%.23


Tests that detect total


antibody, only IgG or only IgM, should demonstrate a minimum PPA of 90% and NPA of 95%.23


12 DECEMBER 2021 MLO-ONLINE.COM


Detecting previous exposure Qualitative antibody assays represent a cost effective and easily implemented way to determine if an individual has been exposed to SARS-CoV-2. The presence of antibodies is indicative of an adap- tive immune response resulting from previous exposure. Thus, a positive SARS- CoV-2 antibody test would be expected for individuals who have had a recent or past infection. To date, all authorized SARS-CoV-2 Ab assays have received EUA with this indication for use. In addition, there are numerous other situations in which Ab assays could be useful in providing information for clini- cal decision-making, but these use cases have not received authorization or ap- proval oby the FDA.


Triaging individuals with severe disease for tMab treatment Monoclonal antibody (tMab) infu- sions have received FDA EUAs to treat COVID-19 in non-hospitalized COVID-19 patients30


and are administered as post-


exposure prophylaxis for individuals who are at high risk for severe disease and who have not been vaccinated, or are expected to have an inadequate immune response to SARS-CoV-2 vaccination.31-33


Monoclo-


nal antibody therapy administration is time sensitive and must start as soon as possible post exposure or within 7 days.31 The presence of SARS-CoV-2 antibodies in these patients could be indicative of an adequate immune response from previ- ous exposure or vaccination. Therefore, individuals with detectable antibod- ies would not be candidates for tMab treatment. There are ongoing studies to examine whether these individuals should be excluded as candidates. Highly sensitive and specific SARS-CoV-2 Ab


assays could identify the presence of pre-existing antibodies in candidate pa- tients for tMab therapy. Performing these tests at the point of care could be used to rapidly inform a clinician’s decision whether to administer therapy. Given that tMab therapy must be administered as soon as possible post-exposure or within a maximum of 7 days,31


a point of care


SARS-CoV-2 Ab test solution has the potential to prove optimal.


Assessing seroconversion post vaccination Vaccines that have received EUA or are in development aim to elicit neutralizing antibodies against SARS-CoV-2.21 The majority (but not all) antibodies to RBD are neutralizing.34


ies to antigens other than RBD tend to recognize the S protein.34


Neutralizing antibod- Therefore, anti-


body tests that utilize RBD and S antigen targets could prove useful for detecting seroconversion post vaccination.21


Cur-


rently, no SARS-CoV-2 Ab test has been authorized by the FDA for this intended use and the FDA does not recommend use of antibody testing for assessing immunity post-vaccination. Studies are currently underway to evaluate SARS- CoV-2 antibody tests for the assessment of post vaccination seroconversion.


Differentiate SARS- CoV-2 previous infection and vaccination


Human infection with SARS-CoV-2 results in antibody development against many different viral proteins, including N, S, and RBD.21


Since vaccination-


induced immunity results in develop- ment of antibodies to only the S and RBD, serology tests could potentially be used to differentiate natural infection


Photo 424099736 by Dr_Microbe @ bigstockphoto.com


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