Update on Antibody Testing for SARS-CoV-2/ COVID-19

Published by Nina Luning Prak, MD, PhD and Judith A. O'Donnell, MD, on February 26, 2021

February 18, 2021 Update

Penn Medicine has different serologic tests for SARS-CoV-2 virus that are orderable in Penn Chart. The newest addition to the antibody testing category is a test to measure receptor binding domain (RBD) IgG and RBD IgA antibodies. Unlike the molecular tests for SARS-CoV-2 that are used to diagnose acute COVID-19 infection, SARS-CoV-2 antibody tests are NOT used in diagnosis of acute COVID-19 illness, but do have other potential clinical applications. This document provides updated information on the types of SARS-CoV-2 antibody testing available, when it may be appropriate to order such testing, and how to interpret the results.

Background on Antibody Testing for SARS-CoV-2 Infection:

In most individuals, exposure to the virus, or receipt of a COVID-19 vaccine, will result in the production of detectable antibodies in the serum within 2 weeks. These antibodies persist for months, with IgG antibodies detected longer than either IgA or IgM antibodies. Some important facts on antibody testing:

  • The antibody response in persons infected with SARS-CoV-2, or vaccinated against this virus, includes the development of several specific antibodies.
  • IgG antibody to the nucleocapsid protein of the virus can be used to determine prior exposure to SARS-CoV-2, but not exposure to a spike protein-based vaccine.
  • IgG antibodies to the RBD of the spike protein are correlated with virus neutralization titers and likely indicate protection from significant infection.
  • Measurement of the IgM antibody response to SARS-CoV-2 is NOT recommended due to its poor specificity.‚Äč

SARS-CoV-2 Antibody Tests Available in PennChart with Interpretation and Uses:
Two clinical lab tests that detect antibodies to SARS-CoV-2 are currently available. Both assays are performed on serum.   

Antibody testing remains a limited resource with only narrow clinical applications and should be reserved for:

  • Determining if an immunocompromised person has mounted an antibody response to natural infection or vaccination.
  • Evaluation of a small subset of patients who present with a history of prior undiagnosed viral infection or post-inflammatory syndrome for which SARS-CoV-2 may have been the cause.
  • Confirmation of negative antibodies in a patient for whom compassionate use monoclonal antibody treatment may be indicated for treatment.

Antibody testing is NOT indicated for:

  • The diagnosis of acute COVID-19 disease
  • Routine determination of protective immunity in normal individuals
  • Determination of protective immunity in healthcare personnel as a mechanism to inform staffing decisions, or to guide decisions around personal protective equipment

It is important to note that persons with positive antibodies may still be able to be infected with SARS-CoV-2, and may also be capable of transmitting the infection to others. Antibody-positive individuals should continue to wear masks, wash their hands and engage in social distancing. If antibody-positive persons have a clinical illness that resembles SARS-CoV-2 infection, they should undergo testing using a molecular test. 

Nina Luning Prak, MD, PhD is a Professor of Pathology & Laboratory Medicine, the Director of the Human Immunology Core Facility, and the Associate Director of the Clinical Immunology Laboratory at the Hospital of the University of Pennsylvania. Judith A. O'Donnell, MD is a Professor of Clinical Medicine and the Director of the Department of Infection Prevention and Control at Penn Presbyterian Medical Center.