Diagnostic Modalities for the Detection of SARS-CoV-2: Principles, Advantages, and Pitfalls Suresh Anand BS, a,†, * Jonath Sujan, a,† Ashwin Kumar N, b & Ilamaran M a a Department of Biomedical Engineering, Rajalakshmi Engineering College, Thandalam, Chennai, Tamil Nadu, India; b Department of Biomedical Engineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, India †These authors contributed equally to this work *Address all correspondence to: Suresh Anand BS, Department of Biomedical Engineering, Rajalakshmi Engineering College, Thandalam, Chennai-602 105, Tamil Nadu, India; Tel.: +91-44-3718-1111; Fax: +91-44-3718-1113, E-mail: sanand.iitm@gmail.com ABSTRACT: The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a signif- icant worldwide health concern in recent months. The world has not dealt with such adversities since World War II. The spread has had a devastating and massive impact on global health, the economy, and people’s everyday lives. With the crisis looming around the world, there is not yet any report of a clinically approved drug effective against this virus or or vaccine that can prevent people from getting infected. In this article, we describe different types of diagnostic tests cur- rently used to detect SARS-CoV-2 infection. We also present an overview of the basic principles involved, advantages, and the pitfalls associated with each technique. This article also provides an insight into various supplementary diagnostic modalities, including recent advancements in sensing technologies and further clinical improvement and novelties to fght this pandemic. KEY WORDS: COVID-19, RT-PCR, computed tomography I. CORONAVIRUSES—A BRIEF HISTORY Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagion spreading throughout the world and a progressing pestilence. Coronavi- ruses (CoVs) constitute the family Coronaviridae, suborder Cornidovirineae, order Nidovirales. 1,2 The club-shaped spikes that project from the outside of the virion are the most conspicuous feature of CoVs. There are four genera in the subfamily, which in- clude Alphacoronavirus (α-CoV), Betacoronavi- rus (β-CoV), Gammacoronavirus (γ-CoV), and Deltacoronavirus (δ-CoV). 3,4 CoVs are enveloped and contain positive-stranded RNA genomes rang- ing in size from 26 to 32 kilobases. 5 SARS-CoV-2 belonging to the genera of β-CoV and α-CoV is known to infect mammals and humans. 6,7 Severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) are two recent viral pneumonia cases caused by β-CoVs. The out- break of SARS was frst registered in China in 2002 and then eventually spread worldwide, resulting in hundreds of deaths with a mortality rate of 11%. 8,9 MERS initially reported in Saudi Arabia in 2012 and gradually spread to other nations, with a 37% fatal- ity rate. 10,11 The viruses presumably emerged from bats in both of these epidemics and then infected humans via other intermediary animal hosts, such as SARS-CoV found in civets (Paguma larvata) and MERS-CoV found in camels. 12,13 A. Epidemiology The infection reportedly originated in Wuhan, in the Hubei province of China, and it has spread to 213 countries and territories. 14 SARS-CoV-2 is likely to have been transmitted to humans through hu- man–animal contact from the so-called wet markets in Wuhan. 15 With the onset of the virus in China, the World Health Organization (WHO) reported 44 pneumonia cases with unknown etiology at the end of December 2019. Chinese researchers have announced a new virus isolated from patient sam- ples that originated at the market. 16 As of January 30, 2020, China confrmed 7,734 cases, and 90 Critical Reviews TM in Biomedical Engineering, 48(4):235 – 260 (2020) 0278-940X/20/$35.00 © 2020 by Begell House, Inc. www.begellhouse.com 235