Updated Provider Guidance on Serologic Testing for SARS-CoV-2

Published by Nina Luning Prak, MD, PhD, on March 15, 2023

March 2, 2023 Update

The Clinical Immunology and Clinical Core labs at the Hospital of the University of Pennsylvania have discontinued serologic testing for SARS-CoV-2. The two tests that were previously performed, COVID-19 (SARS-CoV-2) antibodies (Anti-Nucleocapsid IgG Antibody) and SARS-CoV-2 Serology, antibodies, immunoassay (RBD assessment), are no longer available as in-house assays.

Serum nucleocapsid antibodies were used earlier in the pandemic to evaluate individuals with a history of an undiagnosed viral infection or post-infectious inflammatory syndrome to rule in or out SARS-CoV-2 exposure. At this point, with the diminished virulence of circulating strains of SARS-CoV-2 and increased seroprevalence, the utility of this assay is doubtful. Nucleic acid-based testing rather than serology is the standard of care for the evaluation of possible acute COVID and alternative therapeutic options (such as oral antivirals) are available in patients with increased risk factors for more severe COVID infection. For these reasons, there is little if any clinical utility for the nucleocapsid serology assay at this time.

The RBD assessment assay measured antibodies to the SARS-CoV-2 receptor binding domain (RBD) in the spike protein and was used primarily to evaluate immunocompromised individuals for their ability to respond to spike-based vaccines. The RBD antigen used in this assay is derived from the Wuhan (alpha) strain of SARS-CoV-2, which is several generations removed from the predominant circulating viral strain. Vaccines are now also including other variants such as omicron.  Given the increasing complexity and variability of a patient’s vaccination and viral exposure history at this phase in the pandemic, any serologic assays that measure antibodies targeting the SARS-CoV-2 spike protein (RBD, S1, S2, whole spike etc.) are very challenging to interpret. In any case, antibody levels against the outdated RBD antigen are not necessarily correlated with immune protection. In addition, the anti-RBD monoclonal antibody cocktail of Tixagevimab/Cilgavimab, sold under the brand name Evusheld, is no longer authorized for pre-exposure prophylaxis, as it is not likely to be protective against most circulating strains of SARS-CoV-2. For these reasons, the RBD assay is no longer recommended for clinical use.

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.