Protein-based Approaches for the Diagnosis of COVID-19

Abstract

Serology tests are performed for diagnosis or monitoring of the disease for a possible exposure to certain pathogens. The strategy mainly depends on testing the presence of antigens that belongs to pathogens by binding to its specific antibody from blood or serum samples of the patient. Currently, these tests are in the process of development for the novel coronavirus or another term SARS-CoV2 and reported studies still require confirmation by RT-PCR method. The determination of the specific SARS-CoV2 antibody should develop depending on the immune system's response in the presence of a pathogen. Several studies reported different immunoglobulin types from different patient samples, additional data would indicate more specific outcome to produce detection tests. Serology tests are basically characterized by the neutralization, antigen-antibody reaction, and the appropriate detection stage. The definition of immunoglobulin types after infection is the major step. The development of serology test data related to the SARS-CoV2 being reported fast and updated rapidly. Protein-based viral serological tests are an attempt to be accelerated for diagnosis and changes in the course of infection. In order to determine a protein-based test, virus-dependent antigenic portions must be identified however SARS-CoV2antigenic sites still under investigation. Only the antigenic similarities of the other coronavirus serological tests (such as SARS/MERS CoV) provide the serologic test outcome. Though, the effectiveness of similar coronaviruses is evaluated rapidly and reported. The particular antibody that to be bound to its antigen and act as an "anchor" for protein-based approaches of the SARS-CoV2 are still in research process.

Keywords

• Coronavirus,COVID-19,SARS-CoV2,serology tests

COVID-19 Tanısında Protein Temelli Yaklaşımlar

Abstract

Serolojik testler belirli patojenlere maruziyetin varlığını teşhis etmek ya da seyir takibi amacıyla kullanılan testlerdir. Kan veya serum örnekleri kullanılarak, patojenlere ait antijenlerin varlığı ve spesifik antikorlara bağlanma prensibine göre çalışır. Güncel olarak COVID-19 veya bir diğer deyişle SARS-CoV2 teşhisi ve seroloji testlerine ait bulguların doğrulanması gerçek zamanlı PCR (RT-PCR) tekniği ile yapılmaktadır. SARS-CoV2 seroloji testlerine ilişkin gelişmeler hızlı bir şekilde güncellenmektedir. Özgün SARSCoV2 antikorlarının tayin edilmesi, patojen varlığında immün sistemin oluşturacağı yanıta bağlı olarak geliştirilir. Bugüne kadar yapılan çalışmalarda farklı hastalardan elde edilen örneklerde farklı immünglobülin tiplerinin belirlendiği bildirilmiştir. Bu nedenle öncelikle enfeksiyondan sonra gelişen immünglobülin tiplerinin belirlenmesi önem arz etmektedir. Serolojik testler temelde; nötralizasyon, antijen-antikor reaksiyonu ve belirleme aşamaları ile karakterizedir. Enfeksiyonun hızlı teşhisi ve seyrinin takibi için SARS-COV2 seroloji testleri ile ilgili araştırma ve geliştirme çalışmaları hızla devam etmektedir. Bugüne kadar bildirilen serolojik test sonuçları, benzerlik taşıyan koronavirüs antikor testleri (SARS/MERS-CoV vb) kullanılarak elde edilmiştir. Bu sürecin tamamlanması için virüse bağlı antijenik kısımların tanımlanması gerekmektedir. SARS-CoV2’ye özgül, antijene bağlanacak antikorun, protein temelli yaklaşımlarda bir "çapa" (anchor) olarak kullanılması için araştırmalar devam etmektedir.

Keywords

• Koronavirüs,COVID-19,SARS-CoV2,seroloji testleri

References

1. 1. Xia D WD, Preas C, Schnurr D. Serologic (Antibody Detection) Methods. In: Loeffelholz M HR, Young S, Pinsky B, editor. Clinical Virology Manual. 50 ed. Washington, DC: ASM Press; 2016. p. 105-16.
2. 2. Avivar C. Strategies for the successful implementation of viral laboratory automation. Open Virol J. 2012;6:115-21.
3. 3. EA JA, Jones IM. Membrane binding proteins of coronaviruses. Future Virol. 2019;14(4):275-86.
4. 4. Tang YW, Schmitz JE, Persing DH, Stratton CW. The Laboratory Diagnosis of COVID-19 Infection: Current Issues and Challenges. J Clin Microbiol. 2020.
5. 5. Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg Microbes Infect. 2020;9(1):747-56.
6. 6. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nature Communications. 2020;11(1):1620.
7. 7. Udugama B, Kadhiresan P, Kozlowski HN, Malekjahani A, Osborne M, Li VYC, et al. Diagnosing COVID-19: The Disease and Tools for Detection. ACS Nano. 2020.
8. 8. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020.

9. 9. Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Research and Clinical Practice. 2020;162.
10. 10. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
11. 11. Qian Z, Dominguez SR, Holmes KV. Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation. PLoS One. 2013;8(10):e76469.
12. 12. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARSCoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80 e8.
13. 13. Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, et al. Receptor and viral determinants of SARScoronavirus adaptation to human ACE2. EMBO J. 2005;24(8):1634-43.
14. 14. Infantino M, Damiani A, Gobbi FL, Grossi V, Lari B, Macchia D, et al. Serological Assays for SARS-CoV-2 Infectious Disease: Benefits, Limitations and Perspectives. Isr Med Assoc J. 2020;22(4):203-10
15. 15. Stertz S, Reichelt M, Spiegel M, Kuri T, MartinezSobrido L, Garcia-Sastre A, et al. The intracellular sites of early replication and budding of SARScoronavirus. Virology. 2007;361(2):304-15.
16. 16. Cong Y, Ulasli M, Schepers H, Mauthe M, V’Kovski P, Kriegenburg F, et al. Nucleocapsid Protein Recruitment to ReplicationTranscription Complexes Plays a Crucial Role in Coronaviral Life Cycle. J Virol. 2020;94(4).
17. 17. Tilocca B, Soggiu A, Sanguinetti M, Musella V, Britti D, Bonizzi L, et al. Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses. Microbes Infect. 2020.
18. 18. Klimpel GR. Immune Defenses. In: th, Baron S, editors. Medical Microbiology. Galveston (TX)1996.
19. 19. Basile AJ, Horiuchi K, Panella AJ, Laven J, Kosoy O, Lanciotti RS, et al. Multiplex Microsphere Immunoassays for the Detection of IgM and IgG to Arboviral Diseases. PLOS ONE. 2013;8(9):e75670.
20. 20. Mukherjee S, Dowd KA, Manhart CJ, Ledgerwood JE, Durbin AP, Whitehead SS, et al. Mechanism and significance of cell typedependent neutralization of flaviviruses. J Virol. 2014;88(13):7210-20.
21. 21. Pierson TC, Fremont DH, Kuhn RJ, Diamond MS. Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. Cell Host Microbe. 2008;4(3):229-38.
22. 22. Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. medRxiv April 16, 2020. DOI:10.1101/2020.03.17.20037713
23. 23. Woelfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Mueller MA, et al. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv. March 08,2020: DOI: 10.1101/2020.03.05.20030502
24. 24. Pedersen JC. Hemagglutination-inhibition assay for influenza virus subtype identification and the detection and quantitation of serum antibodies to influenza virus. Methods Mol Biol. 2014;1161:11-25.
25. 25. Nisreen MAO, Ivy W, Wentao L, Corine HG, Elmoubasher ABAF, Mohammed A-H, et al. Serologic Detection of Middle East Respiratory Syndrome Coronavirus Functional Antibodies. Emerging Infectious Disease journal. 2020;26(5):1024.
26. 26. Wu HS, Chiu SC, Tseng TC, Lin SF, Lin JH, Hsu YH, et al. Serologic and molecular biologic methods for SARS-associated coronavirus infection, Taiwan. Emerg Infect Dis. 2004;10(2):304-10.
27. 27. Alexander TS. Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution. Clin Vaccine Immunol. 2016;23(4):249-53.
28. 28. Haveri A, Smura T, Kuivanen S, Osterlund P, Hepojoki J, Ikonen N, et al. Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020. Euro Surveill. 2020;25(11).
29. 29. Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections. 2020;9(1):386-9.
30. 30. To KK-W, Tsang OT-Y, Leung W-S, Tam AR, Wu T-C, 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. The Lancet Infectious Diseases. March 23, 2020. DOI:https://doi.org/10.1016/ S1473-3099(20)30196-1
31. 31. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020 Mar 28. pii: ciaa344. doi: 10.1093/cid/ciaa344. [Epub ahead of print]
32. 32. Health BSoP. Serology testing for COVID-19: Johns Hopkins Center for Health Security; 02/28/2020 [updated 02/21/2020. Available from: https://www. centerforhealthsecurity.org/resources/COVID-19/ COVID-19-fact-sheets/200228-Serology-testingCOVID.pdf.
33. 33. Lv H, Wu NC, Tsang OT-Y, Yuan M, Perera RAPM, Leung WS, et al. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. bioRxiv. March 17,2020: DOI:2020.03.15.993097.
34. 34. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N England J Med. February 28, 2020. DOI: 10.1056/ NEJMoa2002032
35. 35. Nisreen MAO, Marcel AM, Wentao L, Chunyan W, Corine HG, Victor MC, et al. Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease 2019 Patients. Emerging Infectious Disease journal. 2020;26(7).
36. 36. Xiang J, Yan M, Li H, Liu T, Lin C, Huang S, et al. Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold- Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19). medRxiv Marc 01, 2020. DOI:2020.02.27.20028787.
37. 37. Xu Y. Dynamic profile of severe or critical COVID-19 cases. medRxiv. March20, 2020. DOI:2020.03.18.20038513.
38. 38. Maclachlan D, Vogt P, Wu X, Rose L, Tyndall A, Hasler P. [Comparison between line immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies to extractable nuclear antigenes (ENA) with reference to other laboratory results and clinical features]. Z Rheumatol. 2002; 61(5): 534-44.
39. 39. Schüpbach J, Bisset LR, Regenass S, Bürgisser P, Gorgievski M, Steffen I, et al. High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease. BMC Infectious Diseases. 2011;11(1):254.
40. 40. Huang P, Wang H, Cao Z, Jin H, Chi H, Zhao J, et al. A Rapid and Specific Assay for the Detection of MERS-CoV. Front Microbiol. 2018;9:1101.
41. 41. Laksanasopin T, Guo TW, Nayak S, Sridhara AA, Xie S, Olowookere OO, et al. A smartphone dongle for diagnosis of infectious diseases at the point of care. Science Translational Medicine. 2015;7(273):273re1.
42. 42. Rowe T, Abernathy RA, Hu-Primmer J, Thompson WW, Lu X, Lim W, et al. Detection of Antibody to Avian Influenza A (H5N1) Virus in Human Serum by Using a Combination of Serologic Assays. J Clin Microbiol 1999; 37(4): 937.
43. 43. Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 2010;28(6):595-9.
44. 44. Aytur T, Foley J, Anwar M, Boser B, Harris E, Beatty PR. A novel magnetic bead bioassay platform using a microchip-based sensor for infectious disease diagnosis. J Immunol Methods. 2006;314(1):21-9.
45. 45. Bosch I, de Puig H, Hiley M, Carré-Camps M, Perdomo-Celis F, Narváez CF, et al. Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum. Sci Transl Med 2017;9(409): eaan1589.
46. 46. Thaxton CS, Elghanian R, Thomas AD, Stoeva SI, Lee J-S, Smith ND, et al. Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy. Proc Natl Acad Sci USA 2009; 106(44):18437-42.