A Review on the Diagnostic Approaches of COVID-19 Infection; Features and Limitations

10.22122/jims.v39i611.13023

Abstract

Detection of coronavirus disease 2019 (COVID-19) in early stage is indispensible for outcome improvement and interruption of transmission chain. Clear understanding of the nature of the diagnostic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and their challenges, collecting the most diagnostically valuable specimen at the right time from the right anatomic site, and interpretation of their findings is important. This review scrutinizes current challenges and interpretation of reverse transcriptase polymerase chain reaction (RT-PCR), as the reference method, loop-mediated isothermal amplification (LAMP), antibody and antigen detection, typical lung imaging characteristics and prominent abnormal changes in laboratory findings of patients with proven COVID-19, and describes how the results may vary over time. Bronchoalveolar lavage fluid and sputum specimens demonstrate the highest positive rates (93% and 72 %, respectively) in molecular diagnosis of COVID-19. Alternatively, repeated RT-PCR assays can be performed; as over time, it is an increase in the likelihood of the SARS-CoV-2 being present in the nasopharynx. Combining clinical evidence with results of chest computed tomography (CT) and RT-PCR can minimize the risk of diagnostic errors. Elevated levels of interleukin 6 (IL‐6) and D-dimer are thought to be closely associated with the occurrence of severe COVID‐19 in adults, and their combined detection can serve as early factors predicting the severity of COVID‐19. Moreover, elevated acute phase proteins are associated with a poor outcome in COVID-19. Serological diagnosis also is an important tool to understand the extent of COVID-19 in the community, and to identify individuals, who are immune. Antibodies begin to increase from the second week of symptom onset.

Keywords


Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of chest CT and RT-PCR testing for coronavirus disease 2019 (COVID-19) in China: A report of 1014 cases. Radiology 2020; 296(2): E32-E40.
World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance, 25 January 2020. Geneva, Switzerland: World Health Organization; 2020.
Centers for Disease Control and Prevention. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19). Atlanta, GA: CDC; 2021.
Guan Wj, Ni Zy, Hu Y, Liang Wh, Ou CQ, He JX, et al. clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382(18): 1708-20.
National Health Commission of the People's Republic of China. Technical guidance for laboratory testing of 2019-nCoV infection (Third Edition). Biosaf Health 2020; 2(1): 3-5.
World Health Organization. Laboratory biosafety guidance related to coronavirus disease 2019 (COVID-19): Interim guidance, 12 February 2020. Geneva, Switzerland: World Health Organization; 2020.
Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol 2020; 5(5): 434-5.
World Health Organization. Surface sampling of coronavirus disease (COVID-19): A practical "how to" protocol for health care and public health professionals, 18 February 2020. Geneva, Switzerland: World Health Organization; 2020.
Yang Y, Yang M, Shen C, Wang F, Yuan J, Li J, et al. Laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv. 2020.
Centers for Disease Control and Prevention. Real-time RT-PCR Panel for detection 2019-novel coronavirus. Atlanta, GA: Centers for Disease Control and Prevention, Respiratory Viruses Branch, Division of Viral Diseases; 2020.
Chan JF, Yip CC, To KK, Tang TH, Wong SC, Leung KH, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens. J Clin Microbiol 2020; 58(5): e00310-20.
Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med 2020; 58(7): 1070-6.
Lin C, Xiang J, Yan M, Li H, Huang S, Shen C. Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2)-infected pneumonia (COVID-19). Clin Chem Lab Med 2020; 58(7): 1089-94.
Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020; 323(18): 1843-4.
Yu L, Wu S, Hao X, Dong X, Mao L, Pelechano V, et al. Rapid detection of COVID-19 coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform. Clin Chem 2020; 66(7): 975-7.
Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020; 295(1): 202-7.
Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for typical coronavirus disease 2019 (COVID-19) pneumonia: Relationship to negative RT-PCR testing. Radiology 2020; 296(2): E41-E45.
Han R, Huang L, Jiang H, Dong J, Peng H, Zhang D. Early clinical and CT manifestations of coronavirus disease 2019 (COVID-19) pneumonia. AJR Am J Roentgenol 2020; 215(2): 338-43.
Lei J, Li J, Li X, Qi X. CT Imaging of the 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology 2020; 295(1): 18.
Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19). Radiology 2020; 295(3): 715-21.
Li Q, Ding X, Xia G, Geng Z, Chen F, Wang L, et al. A simple laboratory parameter facilitates early identification of COVID-19 patients. medRxiv. 2020.
Rokni M, Ghasemi V, Tavakoli Z. Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS. Rev Med Virol 2020; 30(3): e2107.
Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, et al. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV. Antiviral Res 2017; 137: 82-92.
Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. medRxiv. 2020.
Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta 2020; 505: 190-1.
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020; 506: 145-8.
Rokni M, Ahmadikia K, Asghari S, Mashaei S, Hassanali F. Comparison of clinical, para-clinical and laboratory findings in survived and deceased patients with COVID-19: diagnostic role of inflammatory indications in determining the severity of illness. BMC Infect Dis 2020; 20(1): 869.
Lippi G, South AM, Henry BM. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Ann Clin Biochem 2020; 57(3): 262-5.
Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: A meta-analysis. Ther Adv Respir Dis 2020; 14: 1753466620937175.
Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol 2020; 92(7): 791-6.
Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg Microbes Infect 2020; 9(1): 747-56.
Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: Implication of multiple shedding routes. Emerg Microbes Infect 2020; 9(1): 386-9.
Sethuraman N, Jeremiah SS, Ryo A. Interpreting diagnostic tests for SARS-CoV-2. JAMA 2020; 323(22): 2249-51.
Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin Infect Dis 2020; 71(16): 2027-34.
To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study. Lancet Infect Dis 2020; 20(5): 565-74.
Xiang F, Wang X, He X, Peng Z, Yang B, Zhang J, et al. Antibody detection and dynamic characteristics in patients with coronavirus disease 2019. Clin Infect Dis 2020; 71(8): 1930-4.
Guo L, Ren L, Yang S, Xiao M, Chang, Yang F, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis 2020; 71(15): 778-85.