COVID-19 Clinical Diagnostics and Testing Technology

Abstract

Given the global nature of the coronavirus disease 2019 (COVID-19) pandemic, the need for disease detection and expanding testing capacity remains critical priorities. This review discusses the technological advances in testing capability and methodology that are currently used or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID-19 diagnostics on the horizon. Antibody response against SARS-CoV-2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.

Keywords: COVID-19; RT-PCR; SARS-CoV-2; antibody; antigen; serology.

Figure 1

The SARS‐CoV‐2 viral structure and gene map. SARS‐CoV‐2 is a positive‐stranded RNA virus with a genome size of ∼30 kb encoding genes for non‐structural proteins (ORF1a and ORF1b) involved in replication at the 5′‐end and multiple structural proteins (S, E, M, N) downstream that make up the virus particle. Target‐specific forward and reverse primers are designed to flank regions of interest that are unique to SARS‐CoV‐2. Regions highlighted in red are believed to be those that confer viral pathogenicity. NCBI Reference Sequence: NC_045512 (GenBank accession number MN908947). Figure created with BioRender.com. E = envelop; M = membrane; N = nucleocapsid; ORF1ab = open reading frame; RdRp = RNA dependent RNA polymerase; S = spike; SARS‐CoV‐2 = severe acute respiratory syndrome‐coronavirus 2. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Detection probability of viral RNA or antibody (IgA, IgM, and IgG) against SARS‐CoV‐2 during the course of infection (relative to symptom onset). The testing windows of nucleic acid amplification tests (RT‐PCR, blue) and serology tests (antibody, green) are indicated. Ig = immunoglobulin; RT‐PCR = real‐time reverse transcriptase polymerase chain reaction; SARS‐CoV‐2 = severe acute respiratory syndrome‐coronavirus 2. [Color figure can be viewed at wileyonlinelibrary.com]