Diagnostic Tests for COVID-19.

Tung Phan, Kristin Nagaro
Author Information
  1. Tung Phan: University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  2. Kristin Nagaro: Indiana University School of Medicine, Indianapolis, IN, USA. Kristin.Nagaro@gmail.com.

Abstract

The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ramifications on both an individual level and a public health level. The use of appropriate testing mechanisms is paramount to preventing transmission, along with offering treatment to those who are infected and show appropriate symptomatology. The choice of employing a specific test often relies on laboratory capabilities, including the abilities of the medical technologists, the cost of testing platforms, and the individual quirks of each test. This chapter intends to discuss the relevant issues relating to diagnostic testing for SARS-CoV-2, including specimen types and collection methods, viral detection methods, and serological testing.

Keywords

References

  1. Baden LR, Drazen JM, Kritek PA, Curfman GD, Morrissey S, Campion EW (2009) H1N1 influenza a disease–information for health professionals. N Engl J Med 360:2666–2667 [PMID: 19423873]
  2. Bao L, Deng Q, Gao H et al (2020) Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxIV
  3. Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, Miao X, Streithorst JA, Granados A, Sotomayor-Gonzalez A, Zorn K, Gopez A, Hsu E, Gu W, Miller S, Pan CY, Guevara H, Wadford DA, Chen JS, Chiu CY (2020) CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol 38:870 [PMID: 32300245]
  4. Burbelo PD, Iadarola MJ, Chaturvedi A (2019) Emerging technologies for the detection of viral infections. Future Virol 14:39–49 [PMID: 31933674]
  5. Callahan CJ, Lee R, Zulauf KE, Tamburello L, Smith KP, Previtera J, Cheng A, Green A, Azim AA, Yano A, Doraiswami N, Kirby JE, Arnaout RA (2020) Open Development and Clinical Validation Of Multiple 3D-Printed Nasopharyngeal Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck. J Clin Microbiol 58(8):e00876-20 [PMID: 32393482]
  6. CDC, Centers for Disease Control and Prevention (2020) Interim guidelines for collecting, handling, and testing clinical specimens from persons for Coronavirus disease 2019 (COVID-19). Accessed May 24. https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html
  7. Chan CM, Tse H, Wong SS, Woo PC, Lau SK, Chen L, Zheng BJ, Huang JD, Yuen KY (2009) Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus. J Clin Virol 45:54–60 [PMID: 19342289]
  8. Chen X, Zhou B, Li M, Liang X, Wang H, Yang G, Wang H, Le X (2004) Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis 189:1158–1163 [PMID: 15031782]
  9. Chen C, Gao G, Xu Y, Pu L, Wang Q, Wang L, Wang W, Song Y, Chen M, Wang L, Yu F, Yang S, Tang Y, Zhao L, Wang H, Wang Y, Zeng H, Zhang F (2020a) SARS-CoV-2-positive sputum and Feces after conversion of pharyngeal samples in patients with COVID-19. Ann Intern Med 172:832–834 [PMID: 32227141]
  10. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L (2020b) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395:507–513 [PMID: 32007143]
  11. Chen Y, Chen L, Deng Q, Zhang G, Wu K, Ni L, Yang Y, Liu B, Wang W, Wei C, Yang J, Ye G, Cheng Z (2020c) The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. J Med Virol 92:833–840 [PMID: 32243607]
  12. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brunink S, Schneider J, Schmidt ML, Mulders DG, Haagmans BL, van der Veer B, van den Brink S, Wijsman L, Goderski G, Romette JL, Ellis J, Zambon M, Peiris M, Goossens H, Reusken C, Koopmans MP, Drosten C (2020) Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 25:2000045 [>PMCID: ]
  13. Cox JL, Koepsell SA (2020) 3D-printing to address COVID-19 testing supply shortages. Lab Med 51:e45 [PMID: 32386057]
  14. de Alwis R, Chen S, Gan ES, Ooi EE (2020) Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development. EBioMedicine 55:102768 [PMID: 32344202]
  15. Diagnostics, Copan (2020) UTM: viral transport, Accessed May 13. https://www.copanusa.com/wp-content/uploads/2019/08/UTM-Brochure.pdf
  16. Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S (2009) The spike protein of SARS-CoV–a target for vaccine and therapeutic development. Nat Rev Microbiol 7:226–236 [PMID: 19198616]
  17. FDA, U.S. Food & Drug Administration US (2020) FAQs on testing for SARS-CoV-2, Accessed May 13. https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-testing-SARS-CoV-2
  18. FIND, Foundation for Innovative New Diagnostics (2020) SARS-CoV-2 Diagnostic Pipeline, Accessed May 7. https://www.finddx.org/covid-19/pipeline/
  19. Goyder C, Tan PS, Verbakel J, Ananthakumar T, Lee JJ, Hayward G, Turner PJ, Van Den Bruel A (2020) Impact of point-of-care panel tests in ambulatory care: a systematic review and meta-analysis. BMJ Open 10:e032132 [PMID: 32111610]
  20. Guo L, Ren L, Yang S, Xiao M, Chang FY, Dela Cruz CS, Wang Y, Wu C, Xiao Y, Zhang L, Han L, Dang S, Xu Y, Yang Q, Xu S, Zhu H, Xu Y, Jin Q, Sharma L, Wang L, Wang J (2020a) Profiling early humoral response to diagnose novel Coronavirus disease (COVID-19). Clin Infect Dis 71:778 [PMID: 32198501]
  21. Guo, X, Guo Z, Duan C, Chen Z, Wang G, Lu Y, Li M, Lu J (2020b) Long-term persistence of IgG antibodies in SARS-CoV infected healthcare workers. medRxiv 2020.02.12.20021386. https://doi.org/10.1101/2020.02.12.20021386
  22. Haveri A, Smura T, Kuivanen S, Osterlund P, Hepojoki J, Ikonen N, Pitkapaasi M, Blomqvist S, Ronkko E, Kantele A, Strandin T, Kallio-Kokko H, Mannonen L, Lappalainen M, Broas M, Jiang M, Siira L, Salminen M, Puumalainen T, Sane J, Melin M, Vapalahti O, Savolainen-Kopra C (2020, Mar) Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020. Euro Surveill 25(11):2000266. https://doi.org/10.2807/1560-7917.ES.2020.25.11.2000266
  23. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK, Case Investigation Team Washington State -nCo V (2020) First Case of 2019 novel Coronavirus in the United States. N Engl J Med 382:929–936 [PMID: 32004427]
  24. Hsiung GD (1984) Diagnostic virology: from animals to automation. Yale J Biol Med 57:727–733 [PMID: 6395512]
  25. IDSA, Infectious DIseases Society of America (2020) Infectious Diseases Society of America guidelines on the diagnosis of COVID-19.
  26. Infantino M, Damiani A, Gobbi FL, Grossi V, Lari B, Macchia D, Casprini P, Veneziani F, Villalta D, Bizzaro N, Cappelletti P, Fabris M, Quartuccio L, Benucci M, Manfredi M (2020) Serological assays for SARS-CoV-2 infectious disease: benefits, limitations and perspectives. Isr Med Assoc J 22:203–210 [PMID: 32286019]
  27. Kankaanpaa M, Raitakari M, Muukkonen L, Gustafsson S, Heitto M, Palomaki A, Suojanen K, Harjola VP (2016) Use of point-of-care testing and early assessment model reduces length of stay for ambulatory patients in an emergency department. Scand J Trauma Resusc Emerg Med 24:1–7
  28. Kankaanpaa M, Holma-Eriksson M, Kapanen S, Heitto M, Bergstrom S, Muukkonen L, Harjola VP (2018) Comparison of the use of comprehensive point-of-care test panel to conventional laboratory process in emergency department. BMC Emerg Med 18:43 [PMID: 30453888]
  29. Kim D, Quinn J, Pinsky B, Shah NH, Brown I (2020) Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA 323:2085–2086 [PMID: 32293646]
  30. Kozel TR, Burnham-Marusich AR (2017) Point-of-care testing for infectious diseases: past, present, and future. J Clin Microbiol 55:2313–2320 [PMID: 28539345]
  31. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, Sun R, Wang Y, Hu B, Chen W, Zhang Y, Wang J, Huang B, Lin Y, Yang J, Cai W, Wang X, Cheng J, Chen Z, Sun K, Pan W, Zhan Z, Chen L, Ye F (2020) Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol 92:1518–1524 [PMID: 32104917]
  32. Lieberman JA, Pepper G, Naccache SN, Huang ML, Jerome KR, Greninger AL (2020, Jul 23) Comparison of Commercially Available and Laboratory Developed Assays for in vitro Detection of SARS-CoV-2 in Clinical Laboratories. J Clin Microbiol 58(8):821–20. https://doi.org/10.1128/JCM.00821-20
  33. Loeffelholz MJ, Alland D, Butler-Wu SM, Pandey U, Perno CF, Nava A, Carroll KC, Mostafa H, Davies E, McEwan A, Rakeman JL, Fowler RC, Pawlotsky JM, Fourati S, Banik S, Banada PP, Swaminathan S, Chakravorty S, Kwiatkowski RW, Chu VC, Kop J, Gaur R, Sin MLY, Nguyen D, Singh S, Zhang N, Persing DH (2020) Multicenter evaluation of the Cepheid Xpert Xpress SARS-CoV-2 test. J Clin Microbiol 58:e00926-20 [PMID: 32366669]
  34. Meyer B, Drosten C, Muller MA (2014) Serological assays for emerging coronaviruses: challenges and pitfalls. Virus Res 194:175–183 [PMID: 24670324]
  35. Miller JM, Binnicker MJ, Campbell S, Carroll KC, Chapin KC, Gilligan PH, Gonzalez MD, Jerris RC, Kehl SC, Patel R, Pritt BS, Richter SS, Robinson-Dunn B, Schwartzman JD, Snyder JW, Telford S 3rd, Theel ES, Thomson RB Jr, Weinstein MP, Yao JD (2018) A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the infectious diseases society of America and the American society for microbiology. Clin Infect Dis 67:e1–e94 [PMID: 29955859]
  36. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, Sakata H, Kondo K, Myose N, Nakao A, Takeda M, Haro H, Inoue O, Suzuki-Inoue K, Kubokawa K, Ogihara S, Sasaki T, Kinouchi H, Kojin H, Ito M, Onishi H, Shimizu T, Sasaki Y, Enomoto N, Ishihara H, Furuya S, Yamamoto T, Shimada S (2020) A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 94:55–58 [PMID: 32251791]
  37. Niesters HG (2004) Molecular and diagnostic clinical virology in real time. Clin Microbiol Infect 10:5–11 [PMID: 14706081]
  38. Okba NMA, Muller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, Lamers MM, Sikkema RS, de Bruin E, Chandler FD, Yazdanpanah Y, Le Hingrat Q, Descamps D, Houhou-Fidouh N, Reusken C, Bosch BJ, Drosten C, Koopmans MPG, Haagmans BL (2020) Severe acute respiratory syndrome Coronavirus 2-specific antibody responses in Coronavirus disease patients. Emerg Infect Dis 26:1478–1488 [PMID: 32267220]
  39. Paules CI, Marston HD, Fauci AS (2020) Coronavirus infections-more than just the common cold. JAMA 323:707 [PMID: 31971553]
  40. Peng L, Liu J, Xu W, Luo Q, Chen D, Lei Z, Huang Z, Li X, Deng K, Lin B, Gao Z (2020) SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. J Med Virol 92:1676 [PMID: 32330305]
  41. Phan T (2020) Novel coronavirus: From discovery to clinical diagnostics. Infect Genet Evol 79:104211 [PMID: 32007627]
  42. Qin Q, Wang K, Yang J, Xu H, Cao B, Wo Y, Jin Q, Cui D (2019) Algorithms for immunochromatographic assay: review and impact on future application. Analyst 144:5659–5676 [PMID: 31417996]
  43. Scagnolari C, Turriziani O, Monteleone K, Pierangeli A, Antonelli G (2017) Consolidation of molecular testing in clinical virology. Expert Rev Anti-Infect Ther 15:387–400 [PMID: 28002969]
  44. Storch GA (2000) Diagnostic virology. Clin Infect Dis 31:739–751 [PMID: 11017824]
  45. Theel ES, Slev P, Wheeler S, Couturier MR, Wong SJ, Kadkhoda K (2020) The role of antibody testing for SARS-CoV-2: is there one? J Clin Microbiol 58:e00797-20 [PMID: 32350047]
  46. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W (2020a) Detection of SARS-CoV-2 in different types of clinical specimens. JAMA
  47. Wang X, Tan L, Wang X, Liu W, Lu Y, Cheng L, Sun Z (2020b) Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously. Int J Infect Dis 94:107–109 [PMID: 32315809]
  48. Wang X, Zhong M, Liu Y, Ma P, Dang L, Meng Q, Wan W, Ma X, Liu J, Yang G, Yang Z, Huang X, Liu M (2020c) Rapid and sensitive detection of COVID-19 using CRISPR/Cas12a-based detection with naked eye readout, CRISPR/Cas12a-NER. Sci Bull (Beijing) 65:1436–1439
  49. Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brunink S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C (2020) Virological assessment of hospitalized patients with COVID-2019. Nature 581:465–469 [PMID: 32235945]
  50. Woo PC, Lau SK, Wong BH, Chan KH, Hui WT, Kwan GS, Peiris JS, Couch RB, Yuen KY (2004) False-positive results in a recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid enzyme-linked immunosorbent assay due to HCoV-OC43 and HCoV-229E rectified by Western blotting with recombinant SARS-CoV spike polypeptide. J Clin Microbiol 42:5885–5888 [PMID: 15583332]
  51. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC, Research TSNCO (2020) Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 323:1488 [PMID: 32125362]
  52. Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, Gao G, Wang S, Ma C, Xie R, Wang F, Tan C, Zhu L, Guo Y, Zhang F (2020) Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis 71:793 [PMID: 32221523]
  53. Zhang G, Nie S, Zhang Z, Zhang Z (2020a) Longitudinal change of SARS-Cov2 antibodies in patients with COVID-19′. In: J infect dis
  54. Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, Wang YY, Xiao GF, Yan B, Shi ZL, Zhou P (2020b) Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 9:386–389 [PMID: 32065057]
  55. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, Qian S, Hong C, Wang F, Liu Y, Wang Z, He Q, Li Z, He B, Zhang T, Fu Y, Ge S, Liu L, Zhang J, Xia N, Zhang Z (2020a) Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis 71:2027–2034 [PMID: 32221519]
  56. Zhao R, Li M, Song H, Chen J, Ren W, Feng Y, Gao GF, Song J, Peng Y, Su B, Guo X, Wang Y, Chen J, Li J, Sun H, Bai Z, Cao W, Zhu J, Zhang Q, Sun Y, Sun S, Mao X, Su J, Chen X, He A, Gao W, Jin R, Jiang Y, Sun L (2020b) Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection. Clin Infect Dis 71:2066–2072
  57. Zhen W, Smith E, Manji R, Schron D, Berry GJ (2020) Clinical evaluation of three sample-to-answer platforms for the detection of SARS-CoV-2. J Clin Microbiol 58:e00783-20 [PMID: 32332061]
  58. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W, Coronavirus ICN, Team Research (2020) A novel Coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727–733 [PMID: 31978945]

MeSH Term

COVID-19
COVID-19 Testing
Clinical Laboratory Techniques
Diagnostic Tests, Routine
Humans
SARS-CoV-2

Word Cloud

Created with Highcharts 10.0.0testingSARS-CoV-2detectionindividuallevelappropriatetestincludingtypescollectionmethodsDiagnosticCOVID-19Specimendiagnosissevereacuterespiratorysyndromecoronavirus2ramificationspublichealthusemechanismsparamountpreventingtransmissionalongofferingtreatmentinfectedshowsymptomatologychoiceemployingspecificoftenrelieslaboratorycapabilitiesabilitiesmedicaltechnologistscostplatformsquirkschapterintendsdiscussrelevantissuesrelatingdiagnosticspecimenviralserologicalTestsMolecularSerodiagnosisViral

Similar Articles

Cited By