Diagnosis of SARS-CoV-2 Infection Using Immunoassays: Antigen/Antibody-Based Tests

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced global pandemic, caused by coronavirus disease 2019 (COVID-19), has taken a toll on millions of lives worldwide. Hence, there is an increasing need for accurate disease diagnosis to prevent rapid transmission and provide immediate treatment to patients having mild to severe symptoms of COVID-19 on an urgent basis. Immunoassays are among the several developed techniques for COVID-19 diagnosis. These are generally biochemical tests designed to identify the presence and level of a SARS-CoV-2-specific biomarker employing either antigens (Ags) or antibodies (Abs). Immunoassays rely on a competitive affinity reaction between the target immunological biomarker (Ag/Ab) and other (bio)molecules present in a patient’s sample for the limited binding sites on the immobilised capture molecule (Ab/Ag). Unlike conventional immunoassays, including quantitative/semi-quantitative serology tests that detect circulating anti-SARS-CoV-2 Abs using enzyme-linked immunosorbent assay (ELISA) and/or chemiluminescent immunoassay (ChLIA) techniques, rapid immunoassays, or rapid diagnostic tests (RDTs), are qualitative, simple-to-use assays that utilise an immunochromatographic (lateral flow) test format. Moreover, such tests can be conducted at or near the point of care (PoC) without requiring any high-throughput laboratory infrastructure. Based on the mechanism of detection, SARS-CoV-2 RDTs can be broadly classified into two types, namely (1) Ag tests, which directly identify the SARS-CoV-2 viral Ag(s), and (2) Ab tests that identify one or more variants of antiviral Abs secreted by the host immune system in response to viral infection. Although effective, both techniques have certain limitations. New developments in existing colourimetric lateral flow immunoassays (LFIAs) are underway to address these issues and challenges. Ag-detecting RDTs (Ag-RDTs) are expected to significantly broaden the testing domain, enabling more precise viral load estimation, cost-effective treatment for infected persons, and the formulation of adequate prophylactic measures. In contrast, serology tests [including Ab-detecting RDTs (Ab-RDTs)] could be used for serosurveillance of patients recovered from COVID-19.