**1. Introduction**

SARS-CoV-2 is a positive-sense single-stranded ribonucleic acid (RNA) virus with characteristic spikes on its surface that provide its crown-like appearance. It comprises different structural proteins, namely nucleocapsid protein (NP), spike protein (SP), membrane protein (MP), and envelope protein (EP), which play an important role in the manifestation of SARS-CoV-2 infection (**Figure 1**). The World Health Organisation (WHO), on February 11, 2020, coined the term COVID-19 for the lung disease that SARS-CoV-2 causes. The WHO declared COVID-19 as a public health emergency of international concern (PHEIC) and a pandemic on January 30, 2020, and March 11, 2020, respectively. The pandemic's epicenter shifted from

**Figure 1.** *Schematic of the SARS-CoV-2. Reproduced with permission from MDPI [1].*

China to Europe and then to the United States of America (USA) and many countries during 2020.

SARS-CoV-2, discovered in the Hubei province of Wuhan city in China in December 2019, has spread to 219 countries and territories. The confirmed COVID-19 cases exceed 129 million [2], while global deaths exceed 2.82 million. USA accounts for the most COVID-19 cases, i.e., over 31 million, representing about 24% of global COVID-19 cases. With 12.6 and 12.2 million cases, Brazil and India have the subsequent highest incidence of COVID-19. Some nations, such as Singapore, New Zealand, and China, have effectively controlled the COVID-19 incidence by acting proactively and taking the desired measures at the right time.

The origin of SARS-CoV-2 is still unclear and contradictory, but the early reports mention its transmission to humans at the Wuhan's live animals market in December 2019 [3]. Some researchers claim its origin in bats, although the intermediate hosts are still not identified [4]. The genomic sequence of SARS-CoV-2 has ~82% homology with human SARS-CoV and ~ 89% homology with bat SARS-like CoVZXC21 [5]. The most vulnerable groups at higher risk of developing severe COVID-19 are persons over 65 years of age; persons with chronic diseases, such as diabetes mellitus, hypertension, cardiovascular diseases, lung disease; and decreased immunity. The intensive large-scale testing of the population to identify and quarantine COVID-19 infected persons is essential to avoid the spread of infection. Rapid LFIAs have played a phenomenal role here, and many of such tests have also been approved for self-use [6]. The use of face masks and social distancing measures has played a significant role in preventing COVID-19 infection [7–9]. There has been considerable improvement in the RT-PCR tests, which are the accepted gold standard for confirmatory COVID-19 clinical diagnosis. However, several deficiencies have also been reported where they were unable to detect COVID-19 during the early stages of infection and provided false negatives results to subjects [10, 11]. The false negative results could be due to the improper extraction of nucleic acid from clinical materials or insufficient cellular material for detection. The chest computerized tomography (CT) scan has further helped physicians detect COVID-19 infection in such RT-PCR false-negative subjects [12, 13]. The last year has also seen the emergence of many mutations in SARS-CoV-2 [14–17], which can only be diagnosed by next-generation sequencing (NGS). There are continuous efforts to develop POC biosensor devices for rapid diagnosis of COVID-19. Further,

In Vitro *Diagnostics for COVID-19: State-of-the-Art, Future Directions and Role in Pandemic… DOI: http://dx.doi.org/10.5772/intechopen.97775*

many IVD companies and researchers are working on new IVD approaches, such as detecting specific biomarkers that will enable the detection of COVID-19 infection at a very early stage. There is a need for continuous improvement in IVD assays to ensure reliable detection of SARS-CoV-2 infection without being impacted by the SP mutations.
