**2.6 Rapid diagnostics tests based on detection of antibodies**

This is the most common type of test for the diagnosis for COVID-19. The working principle of this test includes the detection antibodies present in blood sample of people infected from COVID-19. It detects two types of antibodies isotopes namely: IgG and IgM [34]. The development of antibodies and their responses

*Evolution of Diagnostic Methods and Prevalence Detection of COVID-19: A Review DOI: http://dx.doi.org/10.5772/intechopen.99241*

varies from person to person accordingly. Some studies show that antibodies response is detected only in 2nd week from the development of COVID-19 symptoms [35] i.e. during the recovery phase. A COVID-19 antibody-based tests can cross-react with other pathogens, including other human coronaviruses [35, 36], resulting in false-positive results. The timing and type of antibody testing determines accuracy. One of the benefits of this testing is that people who have recovered from COVID-19 will donate their plasma, which is then used to cure those who have serious disease and improve their capacity to combat the virus. These tests can be conducted on blood, serum, or plasma samples, with results available in 30 minutes and a positive result after 7–10 days of infection [36, 37].

#### **2.7 CRISPR/Cas**

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), a rapid approach for diagnosing COVID-19, was recently suggested by scientists and researchers. CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms including bacteria and archaea that function as an immune system against foreign elements in archaea and bacteria. CRISPR is also used potentially to treat genetic diseases and cancer [38]. This approach employs gene-editing technology, which allows for the detection of the coronavirus in just 5 minutes and the delivery of results in just 45 minutes, attracting a lot of interest. The COVID-19 CRISPR test identifies a 20-base RNA sequence by using a "guide" RNA that is complementary to the target RNA sequence and binds to it in the solution. When guide RNA binds to target RNA, CRISPR tools Cas 13 "Scissors" enzyme activates and cuts apart any nearby single – stranded RNA. Such cuts release a fluorescent particle separately in the test solution. The sample is then hit with a laser light and the released fluorescent particle if lighted up indicating the presence of coronavirus. This method for the diagnosis of coronavirus is currently being used by Sherlock Biosciences, US and in India by Tata group under the brand name 'Feluda'. CRISPR does not require specialized or expensive laboratory apparatus and hence can be perfectly deployed in doctor's office, schools and office buildings. Other advantages of this method include its great programmability and its speed [39]. However, there are certain drawbacks to the CRISPR - Cas9 diagnostic technique, such as off-target effects and unexpected mutations, which are a major worry, particularly when it is used for both therapeutic and diagnostic purposes. Because Cas proteins are obtained from prokaryotic origins, in vivo application of these proteins causes toxic effects in the human cells that contain them, as well as immunological activation and the creation of cas protein specific antibodies, which could obstruct the therapeutic application of CRISPR technology [40, 41].

#### **2.8 Biosensors**

Biosensors are new emerging technology for the rapid detection and diagnosis of mass population infected with SARS-CoV-2. Biosensors are made up of chemical or biological receptors that interact with the target analyte directly, as well as a transducer that translates the detection process into a quantitative signal. Biosensors target biological recognition of molecules such as enzymes, nucleic acids or antibodies and contain transducer and a detector detects the interaction with the analyte and generates an output digitally. Biosensors are classified into four types such as electrochemical biosensors, piezoelectric biosensors, thermal biosensors and optical biosensors. In the recent trend of biosensor, RT-LAMP is mediated with Nano particles biosensors (NBS). According to studies, with biosensors, RT-LAMP is less error prone and achieves higher specificity and low false positive result [42].

CRISPR gene editing technology was recently updated as a biological sensor by combining a CRISPR chip with a Field of Effect Transistor (FET) to diagnose COVID-19 in under 40 minutes [40]. Plasmonic Photothermal (PPT) and localized surface plasmon resonance (LSPR), a dual-function plasmonic biosensor, were designed for the ongoing detection of COVID-19 pandemic. For a few covid sequences, the LSPR biosensor has a higher sensitivity, with a detection maximum of up to 0.22 ppm concentration [43]. Biosensors are mostly designed on the basis of surface nucleoproteins. Piezoelectric immune-sensor and thermal biosensor are also being used for detecting the SARS-CoV-2 virus. The electrochemical paper-based biosensor uses the high –ultra charge transfer efficiency AuNPs with magnetic NPs (Fe204). These biosensors are biodegradable, sensitive, simple and economical [44].

In addition to the methods used to diagnose COVID – 19, some innovative techniques are being used to forecast the source and frequency of the virus's spread so that it can be monitored by implementing some mitigation steps, based on various surveys and studies.
