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Diagnosis
Early diagnosis is crucial for controlling the spread of COVID-19. Molecular detection of SARS-CoV-2 nucleic acid is the gold standard. Many viral nucleic acid detec­ tion kits targeting ORFlb (including RdRp), N, E or S genes are con1n1ercially available' ¹,¹⁰⁶-¹⁰⁹• The detection tin1e ranges fron1 several minutes to hours depending on the technology¹:)⁶·¹⁰"',¹⁰⁹-^1II• The molecular detection can be affected by1nany factors. Although SARS-CoV-2 has been detected from a variety of respiratory sources, including throat swabs, posterior oropharyngeal saliva, nasopharyngeal swabs, sputun1 and bronchial fluid, the viral load is higher in lower respiratory tract sam­ ples¹¹•⁹⁶·¹¹²-¹¹⁵• In addition, viral nucleic acid was also found in san1ples from the intestinal tract or blood even when respiratory san1ples were negative¹¹⁶. Lastly, viral load n1ay already drop fron1 its peak level on disease onset⁹⁶·⁴⁷• Accordingly, false negatives can be common when oral swabs and used, and so multiple detection methods should be adopted to confirm a COVID-19 diagnosisw,¹¹⁸• Other detection methods were there­ fore used to overcome this problem. Chest CT was used to quickly identify a patient when the capacity of molecular detection was overloaded in Wuhan. Patients
Initially, the epicenter of the SARS-CoV-2 pandemic was China, which reported a significant number of deaths associated with COVID-19, with 84,458 laboratory-confirmed cases and 4,644 deaths
as of 13 May 2020 (Fig. 4). As of 13 May 2020, SARS-CoV-2 confinned cases have been reported in more than 210 countries apart fro1n China (Fig. 3 and 4) (WHO Situation Report 114) (25, 64). COVID-19 has been reported on all continents except Antarctica. For 1nany weeks, Italy was the focus of concerns regarding the large nu1nber of cases, with 221,216 cases and 30,911 deaths, but now, the United States is the country with the largest number of cases, 1,322,054, and 79,634 deaths. Now, the United Kingdom has even 1nore cases (226,4671) and deaths (32,692) than Italy. A John Hopkins University web platform has provided daily updates on the basic epide1niology of the COVID-19 outbreak




traditional Chinese 1nedicine (TCM). Therefore, the handling of bats for trading purposes poses a considerable risk of transn1itting zoonotic CoV epidetnics (139).
Due to the possible role played by fann and wild ani1nals in SARS-CoV-2 infection, the WHO, in their novel coronavirus (COVID-19) situation report, recommended the avoidance of unprotected contact with both farm and wild animals (25). The live­ anitnal markets, like the one in Guangdong, China, provides a setting for animal coronaviruses to an1phfy and to be trans1nitted to new hosts, like hu1nans (78). Such 1narkets can be considered a critical place for the origin of novel zoonotic diseases and have enonnous public health significance in the event of an outbreak. Bats are the reservoirs for several viruses; hence, the role of bats in the present outbreak cannot be ruled out (140). In a qualitative study conducted for evaluating the zoonotic risk factors a1nong rural co1n1nunities of southern China, the frequent hu1nan-ani1nal interactions along with the low levels of environmental biosecurity were identified as significant risks for the e1nergence of zoonotic disease in local conununities (141, 142).
The co1nprehensive sequence analysis of the

out on the isolated virus confirmed that there is a potential risk for the reen1ergence of SARS-CoV infection fro1n the viruses that are currently circulating in the bat population (105).

CLINICAL PATHOLOGY OF SARS-CoV-2 (COVID-19)

The disease caused by SARS-CoV-2 is also
na1ned severe specific contagious pneumonia (SSCP), Wuhan pneu1nonia, and, recently, COVID-
19 (110). Compared to SARS-CoV, SARS-CoV-2
has less severe pathogenesis but has superior trans1nission capability, as evidenced by the rapidly increasing nu1nber of COVID-19 cases (111). The incubation period of SARS-CoV-2 in fa1nilial clusters was found to be 3 to 6 days (112). The 1nean incubation period of COVID-19 was found to be 6.4 days, ranging frotn 2.1 to 11.1 days (113). Among an early affected group of 425 patients, 59 years was the median age, of which 1nore males were affected
(114). Si1nilar to SARS and MERS, the severity of this nCoV is high in age groups above 50 years (2, 115). Sy1npto1ns of COVID-19 include fever, cough, 1nyalgia or fatigue, and, less conunonly, headache, bemoptysis, and diarrhea (116, 282). Compared to


reduce virus-triggered 11111nune pathologies 111 COVID-19 (209). The later stages of coronavirus­ induced infla1nmatory cascades are characterized by the release of proinflammatory interleukin-1 (IL-1) family 111e1nbers, such as IL-1 and IL-33. Hence, there exists a possibility that the inflammation associated with coronavirus can be inhibited by utilizing anti-inflammatory cytokines that belong to the IL-1 fa1nily (92). It has also been suggested that the actin protein is the host factor that is involved in cell entry and pathogenesis of SARS-CoV-2. Hence, those drugs that modulate the biological activity of this protein, like ibuprofen, might have some therapeutic application in 1nanaging the disease
(174). The plas1na angiotensin 2 level was found to be markedly elevated in COVID-19 infection and was correlated vvith viral load and lung injury. Hence, drugs that block angiotensin receptors may have potential for treating COVID-19 infection
(121). A scientist fro1n Gennany, na1ned Rolf Hilgenfeld, has been working on the identification of drugs for the treat1nent of coronaviral infection since the ti1ne of the first SARS outbreak (19).
The SARS-CoV S2 subunit has a significant function in 1nediating virus fusion that provides ent1y into the host cell. Heptad repeat 1 (HRl) and heptad