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Review
. 2021 Jan 28:8:605702.
doi: 10.3389/fbioe.2020.605702. eCollection 2020.

COVID-19 in-vitro Diagnostics: State-of-the-Art and Challenges for Rapid, Scalable, and High-Accuracy Screening

Zeina Habli  1 , Sahera Saleh  1 , Hassan Zaraket  2   3 , Massoud L Khraiche  1
Affiliations
Review

COVID-19 in-vitro Diagnostics: State-of-the-Art and Challenges for Rapid, Scalable, and High-Accuracy Screening

Zeina Habli et al. Front Bioeng Biotechnol. .

Abstract

The world continues to grapple with the devastating effects of the current COVID-19 pandemic. The highly contagious nature of this respiratory disease challenges advanced viral diagnostic technologies for rapid, scalable, affordable, and high accuracy testing. Molecular assays have been the gold standard for direct detection of the presence of the viral RNA in suspected individuals, while immunoassays have been used in the surveillance of individuals by detecting antibodies against SARS-CoV-2. Unlike molecular testing, immunoassays are indirect testing of the viral infection. More than 140 diagnostic assays have been developed as of this date and have received the Food and Drug Administration (FDA) emergency use authorization (EUA). Given the differences in assasy format and/or design as well as the lack of rigorous verification studies, the performance and accuracy of these testing modalities remain unclear. In this review, we aim to carefully examine commercialized and FDA approved molecular-based and serology-based diagnostic assays, analyze their performance characteristics and shed the light on their utility and limitations in dealing with the COVID-19 global public health crisis.

Keywords: COVID-19; SARS-CoV-2; diagnostics; pandemic; point-of-care; screening; serological immunoassays.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
SARS-CoV-2 structure, genome, and diagnostic targets.
Figure 2
Figure 2
Variation levels of viral load, IgM and IgG post SARS-CoV-2 infection. Data collected from Tan et al. from 67 confirmed COVID-19 patients (both mild and severe cases) (Tan et al., 2020). Viral RNA (amplified ORF1ab gene) was detected in nasopharyngeal swabs using the Qiamp® viral RNA mini kit (QIAGEN, Hilden, Germany). The viral load threshold (black dashed line) indicates the detection limit of this kit corresponding to a cycle threshold value of 38 which is equivalent to 104.577 genomic copies/mL. On the other hand, IgM & IgG titers (anti-SARS-CoV-2 nucleocapsid immunoglobulins) were analyzed in serum samples using ELISA kits (Livzon Diagnostics Inc., Zhuhai, China). The blue and red dashed lines denote the cutoff value for a positive result. The bold lines represent the trends, fitted using smoothing splines in Matlab.
Figure 3
Figure 3
Workflow for nucleic acid-based detection assays.
Figure 4
Figure 4
Serology-based immunoassays for detection of anti-SARS-CoV-2 antibodies.
See this image and copyright information in PMC

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