SARS-CoV-2 antigen tests offer short turnaround time and high specificity but the lower sensitivity relative to nucleic acid testing increases the risk of further transmission by patients with false-negative antigen test results.
Although numerous SARS-CoV-2 antibody detection methods exist, the lack of harmonization and correlation with neutralizing antibodies limits their clinical usefulness.
SARS-CoV-2 antibody titers are higher after vaccination than after a natural infection, but antibody longevity and the frequency at which vaccine re-immunization will be needed remain unknown.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified as the cause of the coronavirus disease 2019 (COVID-19) global pandemic, is a single-stranded RNA virus belonging to the coronavirus family. It consists of structural spike proteins that interact with angiotensin-converting enzyme 2 receptors to infect host cells, nucleocapsid protein that encapsulates the RNA, and envelope protein that surrounds the nucleocapsid.
Commercially available antibody assays have predominantly been developed to target antibodies to either the spike or nucleocapsid proteins. Although the nucleocapsid protein is highly conserved and less susceptible to genetic variation, the spike protein is the target of neutralizing antibodies, which are hypothesized to correlate with immunity.
Despite public health efforts to encourage masking, social distancing, and surveillance testing, the SARS-CoV-2 virus continued to spread at an alarming rate. As a result, significant effort was dedicated to the development of vaccines against SARS-CoV-2. After rapid development and deployment, several manufacturers began clinical trials on their vaccine within just months of the sequencing of the SARS-CoV-2 virus.
All vaccines available at the time of this publication target the spike protein, and immunocompetent individuals who receive the vaccine develop only antispike antibodies. In contrast, after a natural infection, both antispike and antinucleocapsid antibodies are detectable. Additional longitudinal studies are required to determine the longevity of antibodies after a natural infection or vaccination.
The gold standard for diagnosing a SARS-CoV-2 infection is nucleic acid amplification testing with throat or nasopharyngeal swabs.
However, difficulty of sample collection, slow turnaround time owing to batch mode testing and limited instrument availability, and supply chain shortages for reagents and consumables limited the ability to produce quick diagnostic results in many laboratories. As a result, several manufacturers developed rapid antigen-based assays for the diagnosis of SARS-CoV-2. Although these tests offer several logistical advantages, including rapid identification of infected individuals and ease of implementation in a nonlaboratory setting, antigen testing is considered less sensitive than molecular diagnostic techniques. Furthermore, the performance may vary considerably depending on whether it is used to diagnose symptomatic individuals, or to screen for asymptomatic individuals.
The essential role of rapid and accurate clinical laboratory testing has been highlighted during the SARS-CoV-2 global pandemic. In this review, we discuss the design and performance characteristics of commercially available antibody platforms. We then review antibody response after natural infection and after vaccination, with an emphasis on development of the 3 vaccines currently authorized for use in the United States (Pfizer-BioNtech, Moderna, and Janssen Biotech, Inc). Finally, we consider the use of antigen testing as an alternative diagnostic tool to nucleic acid testing. Taken together, we emphasize the essential contributions of laboratory medicine professionals in the global effort to detect, contain, and eradicate SARS-CoV-2.