COVID-19 diagnostic testing: Technology perspective

Abstract

The corona virus disease 2019 (COVID-19) is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 18 million people were infected with a total of 0.7 million deaths in ∼188 countries. Controlling the spread of SARS-CoV-2 is therefore inherently dependent on identifying and isolating infected individuals, especially since COVID-19 can result in little to no symptoms. Here, we provide a comprehensive review of the different primary technologies used to test for COVID-19 infection, discuss the advantages and disadvantages of each technology, and highlight the studies that have employed them. We also describe technologies that have the potential to accelerate SARS-CoV-2 detection in the future, including digital PCR, CRISPR, and microarray. Finally, remaining challenges in COVID-19 diagnostic testing are discussed, including (a) the lack of universal standards for diagnostic testing; (b) the identification of appropriate sample collection site(s); (c) the difficulty in performing large population screening; and (d) the limited understanding of SARS-COV-2 viral invasion, replication, and transmission.

Keywords: COVID-19; SARS-COV-2; diagnostic test; nucleic acid; serum.

FIGURE 1

Confirmed COVID‐19 cases as of August 5, 2020. The graph was obtained from an online interactive dashboard developed by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA ⁵

FIGURE 2

Diagnostic tests that have been approved according by a country's or region's agency of certification. Panels (A‐C) show the nucleic acid and antibody tests that have been approved by different agencies of certification, countries, and technologies, respectively. The data were obtained from the FIND COVID‐19 diagnostics resource center (https://www.finddx.org/covid-19/) on June 9, 2020. Abbreviations: EUA, Emergency Use Authorization; HSA, Health & Safety/Sciences Authority; MFDS, Ministry of Food & Drug Safety; MHRA, Medicines & Health Care Products Regulatory Agency; NRA, National Regulatory Authority; RUO, Research Use Only; TGA, Therapeutic Goods Administration; WHO EUL, World Health Organization Emergency Use Listing Procedure

FIGURE 3

Schematic illustration of nucleic acid and serum testing methods. Panels (A‐E) are the assay principles of NGS, RT‐PCR, RT‐LAMP, ELISA, CLIA, and LFIA, respectively

FIGURE 4

Comparison of different technologies used for serological antibody detection. The data was obtained from the Kontou study by meta‐analysis of antibody testing in 7848 individuals. ⁵⁴

FIGURE 5

Schematic illustration of promising technologies for SARS‐CoV‐2 detection. (A‐C) are the assay principles of dPCR, CRISPR, and SARS‐CoV‐2 proteome peptide microarray, respectively