Laboratory evaluation of SARS-CoV-2 in the COVID-19 pandemic

Abstract

Laboratory evaluation of SARS-CoV-2 involves the detection of viral nucleic acid, viral protein antigens, and the antibody response. Molecular detection of SARS-CoV-2 is the only diagnostic test currently available in acutely or recently infected individuals. In contrast, serological testing is typically performed once viral RNA has been cleared and symptoms have resolved. This leads to some confusion among clinicians as to which test to order and when each is appropriate. While SARS-CoV-2 assays can suffer from poor sensitivity, all FDA authorized assays to date are intended to be qualitative. Serological tests have multiple assay formats, detect various classes of immunoglobulins, and have a distinct role in seroprevalence studies; however, the association with long-term protection remains unclear. Both molecular and serological testing for SARS-CoV-2 have complementary roles in patient management, and we highlight the challenges faced by clinicians and laboratorians alike in the evaluation and interpretation of the currently available laboratory assays.

Keywords: Analytical sensitivity; COVID-19; Clinical sensitivity; Molecular diagnostics; SARS-CoV-2; Serology.

Fig. 1

SARS-CoV-2 belongs to the betacoronavirus genus. The relationship between other human pathogenic coronaviruses is shown. These similarities highlight the need for specific molecular and serologic detection assays.

Fig. 2

Genomic organization of SARS-CoV-2 based upon Genbank sequence NC_045512.2. Numbers in parenthesis indicate nucleotide length. Genes targeted by current molecular diagnostic assays are depicted with an arrow, proportional in size to the percentage (above arrow) of assays that target the gene. ORF1ab is the largest open reading frame comprising >70% of the genome. Figure not drawn to scale.

Fig. 3

Common pre-analytical issues faced by clinicians and the diagnostic lab stem from supply chain shortages and uncertain clinical case definitions of COVID-19.