Serological Diagnostics for SARS-CoV-2 Infections

Serological diagnostics for SARS-CoV-2 involve the detection and quantification of antibodies generated in response to infection or vaccination. Unlike molecular tests that identify viral RNA during acute infection, serology assays reveal past exposure and the strength of the humoral immune response. These methods underpin epidemiological surveillance, assessment of population-level immunity and evaluation of vaccine performance. Key targets include immunoglobulin M (IgM), immunoglobulin G (IgG) and neutralising antibodies directed against viral antigens such as the spike protein, its receptor-binding domain (RBD) and the nucleocapsid protein. Serological platforms range from laboratory-based enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs) to point-of-care lateral flow tests and emerging biosensor technologies. Recent advances have improved assay sensitivity and specificity, shortened turnaround times and enabled multiplexed detection. Continued development focuses on harmonising quantitative outputs against international standards, extending assay durability to detect antibody waning, and integrating digital-readout systems for decentralised testing. As pandemic response evolves, robust serological diagnostics remain essential for tracking variant-specific immunity, guiding booster strategies and informing public health policy.

Research from Nature Portfolio

Detailed comparative analyses of serological assays have highlighted considerable performance variability across platforms and antigens. One foundational study evaluated multiple commercial and in-house ELISAs, demonstrating that assays targeting total immunoglobulins to the RBD of the spike protein provided the most reliable correlation with virus-neutralising activity. This work established the importance of assay validation against functional neutralisation assays and proposed cut-off values indicative of protective immunity. The study also underscored the need for standardised reagents and international reference panels to align quantitative titres across laboratories and assay formats, thereby enhancing comparability in both clinical diagnostics and large-scale sero-epidemiological surveys.

Serological Diagnostics for SARS-CoV-2 Infections publication trend

The graph below shows the total number of articles in serological diagnostics for sars-cov-2 infections across all publications each year (not limited to Nature Index journals).

Technical terms

Serological assay: A laboratory or point-of-care test that detects and measures antibodies in blood or other bodily fluids to determine immune response to a specific antigen.

Enzyme-linked immunosorbent assay (ELISA): A plate-based immunoassay that uses enzyme-conjugated antibodies to quantify target antibodies or antigens through a colourimetric or fluorescent readout.

Neutralising antibody: An antibody that inhibits viral entry or replication by blocking key interactions, often measured in cell-based neutralisation assays.

Lateral flow assay: A rapid point-of-care immunochromatographic test that visually indicates the presence of target antibodies or antigens through coloured lines on a test strip.

Receptor-binding domain (RBD): A region of the SARS-CoV-2 spike protein that binds to the host cell receptor ACE2; a primary target for neutralising antibodies and serological assays.

Capacitance measurement: An electrochemical technique that detects changes in electrical properties at an electrode surface when biomolecules bind, enabling label-free sensing.

References

1. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nature Communications (2020).
2. Label-free impedimetric immunosensor for point-of-care detection of COVID-19 antibodies. Microsystems & Nanoengineering (2023).
3. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods (2023).
4. Proof-of-Concept: Smartphone- and Cloud-Based Artificial Intelligence Quantitative Analysis System (SCAISY) for SARS-CoV-2-Specific IgG Antibody Lateral Flow Assays. Biosensors (2023).