Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control

Abstract

Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control.

Keywords: COVID-19; SARS-CoV-2; antibodies; detection; immunoassays; nucleocapsid; receptor binding domain; spike.

Figure 1

Schematic diagram of SARS-CoV-2 virus structure and genome organization. (A) The viral surface proteins, spike (S), envelope (E), and membrane (M) are embedded in a lipid bilayer. The single stranded positive-sense viral RNA is associated with the nucleocapsid (N) protein. Diagram was created with BioRender. (B) The genome organization of SARS-CoV-2 viral RNA, which is adapted from GenBank accession number: MN908947, is characterized by sequence alignment against two representative members of the betacoronavirus genus. The entire genome sequence is ~30 kilobases (kb) long.

Figure 2

Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. Presence of SARS-CoV-2 viral RNA (boxed in pink) in throat or nasal swab of patients are typically undetectable by 14 day post illness onset (pio) (8, 9). SARS-CoV-2-specific antibodies (boxed in blue): IgM is detectable as early as 3 days pio, and peaks between 2 and 3 weeks pio (10, 11). IgM response was still detectable after more than 1 month pio (12). Both IgA and IgG are present as early as 4 days pio, and peaks after 2 weeks pio in serum samples (10, 11, 13, 14). There are currently no reports on the presence of these SARS-CoV-2-specific antibodies in the later phase pio, as indicated by dotted lines. This depicts the importance of serological studies to identify individuals with current or prior exposure to SARS-CoV-2 that went undetected, by testing for either IgM, IgG, or IgA antibodies against SARS-CoV-2. Illustration was created using BioRender.