key: cord-1033123-woo0rawx authors: Zalzala, Haider Hashim title: Diagnosis of COVID-19: Facts and challenges date: 2020-09-16 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2020.100761 sha: 446e9d3c3102b58486654fd7021ba0146161a1c5 doc_id: 1033123 cord_uid: woo0rawx At the end of 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, and then spread rapidly across the country and throughout the world. The causative agent is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); according to the International Committee on Taxonomy of Viruses, this virus has a nucleic acid sequence that is different from other known coronaviruses but has some similarity to the beta coronavirus identified in bats. Coronaviruses are a large virus group of enveloped positive-sense single-stranded RNA. They are divided into four genera—alpha, beta, delta, and gamma—and alpha and beta coronaviruses are known to infect humans. Rapid and early diagnosis of COVID-19 is a challenging issue for physicians and other health care personnel. The sensitivity and specificity of the clinical, radiological, and laboratory tests used to diagnose COVID-19 are variable and largely differ in efficacy depending on the patient’s stage of presentation. used for COVID-19 diagnosis (13) . The implemented strategy was to explore the relevant publications indexed by Google Scholar, PubMed, and/or Science Direct databases. Keywords, such as SARS-CoV-2, COVID-19, lateral flow immunoassay, ELISA, PCR, LAMP, CRISPR, were used to search for publications between the December 2019 and July 2020. Approximately 230 articles related to the keyword used were produced at the initial search. But, only 10 articles were obtained after searching within the scope of the current review and excluding the books, duplicates, abstracts, conference proceedings, case report. The decision to test should be based on clinical and epidemiological factors and linked to an assessment of the likelihood of infection(14). It is well known that both innate and adaptive immunity play roles in controlling SARS-CoV-2 infection. In addition, adaptive immunity creates a memory immunity that helps prevent reinfection. One of the components of adaptive immunity is humoral (B-cell or antibody) mediated immunity, which is very important in the clearance of the virus and the prevention of reinfection through the memory immune response. The B-cell immune response elicits a virus-specific antibody response, including immunoglobulin M (IgM), IgG, IgA, and neutralizing IgG antibodies, in the days following SARS-CoV-2 infection (15) . In most COVID-19 patients, antibodies appear 7-14 days after infection and persist for weeks after viral clearance (16) (17) (18) . The most commonly detected antibodies are against the internal N protein and the external S protein, such as a neutralizing J o u r n a l P r e -p r o o f antibody targeted against the receptor binding domain (RBD) of the S protein, which is highly immunogenic, (19) (20) . The difficulty in controlling the spread of COVID-19 stems from the fact that some patients, especially those with high viral loads, can transmit the virus to others despite being asymptomatic (21) .Therefore, urgent and rapid tests are needed to solve this problem. Li (24) showed that the median seroconversion times for nAb, IgM, andnAb, IgM and IgG were at days 11, 12, and 14, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% Enzyme-linked immunosorbent assay (ELISA) is a commonly used technique for which is only approved for use at MSL; and LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin, Inc., Stillwater, MN) (31) . Regarding ELISA specificity, a European study showed that IgG and IgA specificity levels against recombinant structural protein (S1) from SARS-CoV-2 were 91.9% and 73%, respectively (32). This unique technology, which is a variant of ELISA, allows for the multiplexing of several antigens. It is based on magnetic carboxylated microspheres; to which viral antigen(s) attach, and antibodies against the antigen, if present in the patient's serum, can be detected by adding a fluorescently labeled secondary antibody. Both ELISA and microsphere immunoassay (MIA) are more sensitive and specific than lateral flow immunoassays, but they require a longer time for results to become available (five hours for ELISA and three to eight hours for MIA)(31). Attempts to diagnose COVID-19 using antigen detection have been made. Since the opening of the genetic sequences of SARS-CoV-2, molecular diagnosis by nucleic acid amplification using real-time reverse Loop mediated isothermal amplification (LAMP) is a single tube technique for amplification of DNA, and RT-LAMP is used for detection of RNA (49) .In contrast to PCR, the reaction is carried out at a constant temperature. Studies have shown that the technique has good sensitivity and specificity. Kitagawa et al. Clusters of regularly interspaced short palindromic repeats (CRISPR) is a family of DNA sequences found in the genomes of prokaryotic organisms, such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that have previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections (56) . The CRISPR-Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements, such as those present within plasmids and phages (57) CXR is an important tool in the diagnosis of pneumonia, lung abscess, and many other lung diseases. It is readily available in any hospital, and the results can be obtained within minutes (64). patients are multifocal and peripheral and are associated with interstitial and alveolar opacities. Lung lesions primarily manifested as interstitial opacities (71.7%) or alveolar opacities (60.5%) and were frequently bilateral (64.5%) or peripheral (62.5%). Patients admitted to the emergency radiology department more than five days after symptom onset more frequently had interstitial and alveolar opacities than those admitted within five days, and lung lesions were more frequently bilateral and peripheral. Older patients more frequently had interstitial and alveolar opacities than younger ones and a higher rate of pleural effusion (77.1% vs. 22.9%) (66). Although CXR is a simple and rapid radiological test for diagnosis in suspected COVID-19 cases, certain findings, such as infiltrate, patchy, or hazy opacity pneumonia, remain difficult to interpret(67)(68). The predominant CT scan findings in COVID-19 patients are bilateral, peripheral, and basal predominant ground glass opacity; consolidation; or both (69) (70) . Although CT scan sensitivity is high (98%) with low specificity , It may aid but not replace the molecular method for the diagnosis (71) and is considered an important tool to diagnose complications and to graduate the severity of the disease in order to improve the quality of care (72) . Another important aspects of a CT scan is that it is very useful in the diagnosis of asymptomatic patients with COVID-19-related pneumonia and in early stage of the disease (73) . However, CT scans are not J o u r n a l P r e -p r o o f effective for patients who are asymptomatic, presymptomatic, or have mild symptoms without pneumonia (74) . The limitation of using CT scan is that it only available in large hospitals; and images need to be checked by two radiologists. Molecular tests for nucleic acid detection are considered as gold standard method for laboratory diagnosis of COVID-19 disease. They are highly sensitive and specific techniques that can be used as the first line in the diagnosis of acutely infected COVID-19 patients. rtRT-PCR is the mostly commonly used technique; however, it may be not available in low-income countries due to high costs and the need for sophisticated instruments and qualified technicians. Alternatives, such as the LAMP and CRISPR-Cas system techniques, may be considered in those countries because they are low-cost, simple procedures and because manufacturers J o u r n a l P r e -p r o o f have received authorization from the FDA. Antigen detection techniques have lower sensitivity than molecular detection techniques, but the former are easier and require less time for the results to become available. Antibody detection methods, such as lateral flow IC, ELISA, and MIA, can be used for the supplementary detection of SARS-CoV-2 in cases that test negative for nucleic acids, especially seven days after symptom appearance. These methods can be used to track disease progression but have limitations since they cannot detect whether the patient is still infectious. Although lateral flow IC is rapid and requires no technical skills, it has low sensitivity; ELISA and MIA have high sensitivity but take a longer time to perform and require qualified technicians. CXR is simple and accessible, and it can be used as the first and primary imaging technique for COVID-19 patients even though it may give false positive results in mild lung lesions. A CT scan has a sensitivity of 98%, and it aid in the diagnosis of patients with asymptomatic pneumonia; however, it is of no benefit in the diagnosis of patients who are asymptomatic or presymptomatic or have mild symptoms without pneumonia. This work did not receive any grants from funding agencies in the public, commercial, or not-for-profit sectors. J o u r n a l P r e -p r o o f The sensitivity of this rapid test is poor, and improvements are needed to enhance its performance. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 Origin and evolution of pathogenic coronaviruses Human coronavirus circulation in the United States Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. 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