Measuring the Serologic Response to Severe Acute Respiratory Syndrome Coronavirus 2: Methods and Meaning

Abstract

The entire spectrum of diagnostic testing, from reagent supply to test performance, has been a major focus during the coronavirus disease 2019 (COVID-19) pandemic. The hope for serologic testing is that it will provide both epidemiologic information about seroprevalence as well as individual information about previous infection. This information is particularly helpful for high-risk individuals who may be outside of the viral shedding window, such as children with suspected multisystem inflammatory syndrome. It is not yet understood whether serologic testing can be interpreted in terms of protective immunity. These concerns must be addressed using highly sensitive and specific tests.

Keywords: COVID-19; COVID-19 serology; SARS-CoV-2.

Fig. 1

The SARS-CoV-2 genome: SARS-CoV-2 isolate Wuhan-Hu-1, complete genome (NC_045512). Genes encoding nonstructural proteins are shown in gray. Genes encoding structural proteins S, E, M, and NP are shown in blue. ORF, open reading frame.

Fig. 2

Alignment of the S protein among closely related betacoronaviruses: peptide sequences from SARS-CoV-2 (NCBI [National Center for Biotechnology Information] YP_009724390), RaTG13-CoV (NCBI QHR63300), and SARS-CoV-1 (NCBI BAE93401) were aligned using ClustalW. Conserved residues (3/3) are shown in dark blue, (2/3) in teal, (1/3) in gray. The S1/S2 cleavage site is indicated by a red star. The receptor-binding motif is designated by the red line.

Fig. 3

Alignment of the NP protein among closely related betacoronaviruses: peptide sequences from SARS-CoV-2 (NCBI YP_009724390), RaTG13-CoV (NCBI QHR63300), and SARS-CoV-1 (NCBI BAE93401) were aligned using ClustalW. Conserved residues (3/3) are shown in dark blue, (2/3) in teal, (1/3) in gray.

Fig. 4

Conservation of surface amino acids between SARS-CoV-2, SARS-CoV-1, and CoV-OC43: (A) space-filling model of the NP protein RNA-binding region (PDB [Protein Data Bank] 6M3M) and dimerization region (PDB 2GIB) from SARS-CoV-1 with sequence conservation mapped on the surface projection from ClustalW alignments between SARS-CoV-1 (NCBI BAE93401), SARS-CoV-2 (NCBI YP_009724390), and CoV-OC43 (NCBI YP_009555245). (B) Space-filling model of the full-length SARS-CoV-2 S protein monomer (PDB CVYB) with sequence conservation mapped on the surface projection from ClustalW alignments from SARS-CoV-2 (NCBI YP_009724390), SARS-CoV-1 (NCBI BAE93401), and CoV-OC43 (NCBI YP_009555241).