key: cord-0998605-9204b4mx authors: Cui, Feiyun; Zhou, H. Susan title: Diagnostic methods and potential portable biosensors for coronavirus disease 2019 date: 2020-06-02 journal: Biosens Bioelectron DOI: 10.1016/j.bios.2020.112349 sha: 07b40b168b958e00cf0ffb5324d12afdbe446112 doc_id: 998605 cord_uid: 9204b4mx Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical biosensor, surface enhanced Raman scattering (SERS)-based biosensor, and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed. Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection 26 control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of 27 coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 28 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection 29 methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most 30 patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection 31 methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction 32 (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine 33 research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. cost diagnostic tools to screen infected individuals so that proper isolation and treatment can be facilitated. 57 Diagnostic cases of CT scan, various RNA detection methods and antibody detection methods are also 74 summarized and discussed. More interestingly, AI assisted diagnosis and potential ultrasensitive 75 biosensor are emphasized. A comprehensive schematic diagram of current diagnostic methods and 76 potential portable biosensors for COVID-2019 is presented in Figure 1 . Structural proteins, including spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and 134 nucleocapsid (N) protein, and also several accessory proteins. 135 Detection of specific antibodies directed to SARS-CoV-2 in patient blood is another choice for 137 diagnosis of COVID-19. It is widely accepted that immunoglobulin M (IgM) provides the first line of 138 defense during viral infections, prior to the generation of adaptive, high affinity immunoglobulin G (IgG) 139 responses which are responsible for immunological memory and long-term immunity ). 140 diagnostic factors which are significantly related to positive COVID-19 diagnosis were revealed. Among 159 them, white blood cell count (WBC), eosinophil count, eosinophil ratio, 2019 new Coronavirus RNA 160 (2019n-CoV) and serum amyloid A (SAA) have the greatest clinical significance. Some cytokines were 161 also be tested and analyzed and the results showed their levels are abnormal, but the linkage to 162 SARS/MERS is not so significant. However, another study shows that the level of interleukin-6 (IL-6), 163 IL-10, IL-2 and interferons-γ (IFN-γ) in the peripheral blood of the severe cases increased compared to 164 those in the mild cases. The degree of lymphopenia and a proinflammatory cytokine storm is higher in 165 severe COVID-19 patients than in mild cases, it is associated with the disease severity (Liu et Specimens are highly related to detection efficiency and accuracy. Now, specimens from the upper 172 respiratory tract (contain throat, nasal deep throat saliva), lower respiratory tract (contain sputum and 173 bronchoalveolar lavage fluid), feces, fibrobronchoscope brush biopsy, and blood are being investigated. 174 For the RT-qPCR based RNA detection, specimens from the lower respiratory tract induce a relatively loads than that of the throat (Zou et al. 2020 ). Although the nasopharyngeal or throat swabs are feasible 177 for diagnosis, the sampling process can make the patient or suspected case uncomfortable and induce 178 coughing and sneezing, which generates aerosol and creates a potential health hazard for medical staff. 179 Another study reveals that sputum swabs (76.9 %) showed a significantly higher positive rate than throat Table 2 . 191 In conclusion, deep throat saliva and induced sputum are desired for RT-qPCR tests. However , 192 developing methods which allow the patient to collect the samples by themselves are more desirable. simultaneously. This method is now being applied for SARS-CoV-2 protein detection. 89 Ultrasensitive and specific laboratory diagnostic method and portable devices are critical for 2 controlling the rapidly evolving SARS-CoV-2-associated COVID-19 pandemic. Nowadays, CT scan, RT-3 qPCR, and LFICS based on Au NPs colloid (colloidal gold method) have been developed. Many 4 diagnostic kits or strips have been cleared in China for laboratory detection of SARS-CoV-2 (Loeffelholz 5 and Tang 2020). Unfortunately, due to an overwhelming situation in local hospitals at the severe outbreak 6 areas, many suspected cases cannot be efficiently confirmed. Hence, more reliable, rapid, low-cost and 7 widely available diagnostic tools or detection strategies are needed. (1) For early diagnosis, on-site, fast, 8 and ultrasensitive biosensors targeting virus antigen detection has a great potential. They can be used in 9 hospitals, clinics, test laboratories, and even at home, airports or other high traffic areas. The novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal amplification assay. Loop -mediated isothermal amplification. * means specificity to SARS-CoV-2 versus alphacoronavirus (hCoV-229E), betacoronavirus (hCoV-OC43) and MERS-CoV. 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