Potenciales usos, desafíos y limitaciones de la determinación de anticuerpos anti-SARS-CoV-2

Inicio>>Volumen>>Vol 26, N ° 2 mayo – agosto 2021>>Potenciales usos, desafíos y limitaciones de la determinación de anticuerpos anti-SARS-CoV-2

Potenciales usos, desafíos y limitaciones de la determinación de anticuerpos anti-SARS-CoV-2


Autores


Josué Solano-Cerdas, Marvin Durán-Delgado

Resumen


La detección oportuna de personas infectadas con el SARS-CoV-2 resulta fundamental en el abordaje y control de la enfermedad pandémica COVID-19 que ha atacado al mundo desde finales del 2019. La técnica RT-PCR representa la metodología de referencia diagnóstica, sin embargo, el surgimiento de determinaciones serológicas ha brindado una importante herramienta de apoyo en sensibilidad diagnóstica al trabajarse en conjunto con técnicas moleculares. Un papel fundamental de las pruebas serológicas se basa en la posibilidad de evaluar títulos de anticuerpos provenientes de exposiciones previas al SARS-CoV-2 o de tratamiento vacunal. Para poder entender la importancia y dar un correcto uso a las pruebas serológicas, se debe conocer la composición proteica del virus, su interacción con el organismo humano y la respuesta antiviral que se produce. En el presente trabajo, se revisarán los métodos serológicos disponibles para detectar anticuerpos anti-SARS-CoV-2, así como el perfil de seroconversión y los posibles usos de las pruebas serológicas, al igual que sus limitantes; se finaliza con una serie de recomendaciones que podrían optimizar la aplicación de estas pruebas en nuestra población.

Palabras clave

Serología, COVID-19, inmunoensayo, anticuerpos neutralizantes

Abstract


Early detection of people infected with SARS-CoV-2 is essential in the approach and control of the global pandemic COVID-19 disease that has attacked the world since December 2019. The RT-PCR technique represents the diagnostic reference methodology; however, the emergence of serological determinations has provided an important support tool in diagnostic sensitivity when working in conjunction with molecular techniques. A fundamental role of serological tests is based on the possibility of evaluating antibody titers from previous exposures to SARS-CoV-2 or from vaccine treatment (in the future). In order to understand the importance and correct use of serological tests, it is necessary to know the protein composition of the virus, its interaction with the human body and the antiviral response that occurs. The present work reviews the serological methods available to detect Anti SARS-CoV-2 antibodies, as well as the seroconversion profile and the possible uses of serological tests, as well as their limitations; ending with a series of recommendations that could optimize the application of these tests in our population.


Key words

Serology, COVID-19, immunoassay, neutralizing antibodies

Texto completo

VER PDF



Referencias

1. Zhu N, et al. A novel coronavirus from patients with pneumonia in China. N. Engl. J. Med. 2019; 382 (8), 727–733.
2. Jiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol. 2020; 41 (5), 355–359.
3. Siddiqi HK, Mehra,MR. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal. J. Hear. Lung Transplant. 2020; 39 (5), 405–407.
4. Wu Z, McGoogan JM. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA - J. Am. Med. Assoc. 2020; 323 (13), 1239–1242.
5. Van Doremalen N, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N. Engl. J. Med. 2020; 382 (24), 1564–1567.
6. CCSS. COVID-19 CCSS | Estadísticas. (2020). Disponible en: https://www.ccss.sa.cr/web/coronavirus/estadistica.
7. Petherick A. Developing antibody tests for SARS-CoV-2. Lancet. 2020; 395 (10230), 1101–1102.
8. Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection. Ann. Intern. Med. 2020; 173 (5), 362-367.
9. Ivashkiv LB, Donlin,LT. Regulation of type i interferon responses. Nat. Rev. Immunol. 2014; 14 (1), 36–49.
10. Thevarajan Irani, LS. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat. Med. 2020; 26 (4), 450–452.
11. Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerg. Microbes Infect. 2020; 9(1), 727–732.
12. Tay MZ, Poh CM, Rénia L, MacAry, PA Ng, FP. The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 2020; 20(6), 363–374.
13. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019; 17(3), 181–192.
14. Sethuraman N, Jeremiah SS, Ryo, A. Interpreting Diagnostic Tests for SARS-CoV-2. Jama. 2019; 323 (22), 2249-2251.
15. Burbelo PD, et al. Sensitivity in Detection of Antibodies to Nucleocapsid and Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Coronavirus Disease 2019. J. Infect. Dis. 2020; 222(2), 206–213.
16. Okba N. et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg. Infect. Dis. 2020; 26(7), 1478–1488.
17. Krammer F, Simon V. Serology assays to manage COVID-19. Science. 2020(6495); 368, 1060–1061 (2020).
18. Wu F, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered 2 patient cohort and their implications. medRxiv https://doi.org/10.1101/2020.03.30.20047365 (2020).
19. Yan R, Zhang Y, Guo, Y, Xia L, Zhou Q. Structural basis for the recognition of the 2019-nCoV by human ACE2. Science 2020; 2762, 1–10.
20. Vabret N, et al. Immunology of COVID-19: current state of the science. Immunity 2020. doi:10.1016/j.immuni.2020.05.002
21. Brochot E, et al. Anti-Spike anti-Nucleocapsid and neutralizing antibodies in SARS-CoV-2 hospitalized patients and asymptomatic carriers. Medrxiv. 2020; 1–25. doi:10.1101/2020.05.12.20098236
22. Wölfel R, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809), 465–469.
23. To KK, 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), 565–574.
24. Wang , et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA - J. Am. Med. Assoc. 2020; 323(18), 1843–1844.
25. Zhao J, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin. Infect. Dis. 2020; 71(16), 1–22. doi:10.1093/cid/ciaa344
26. Whitman JD, et al. Test performance evaluation of SARS-CoV-2 serological assays. medRxiv Prepr. Serv. Heal. Sci. 2020; 29, 30.
27. FDA. EUA Authorized Serology Test Performance | FDA. (2020). Disponible en: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance. (Accessed: 9th September 2020)
28. FIND. FIND evaluation update: SARS-CoV-2 immunoassays - FIND. (2020). Disponible en: https://www.finddx.org/covid-19/sarscov2-eval-immuno/. (Accessed: 9th September 2020)
29. Nie J, et al. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg. Microbes Infect. 2020; 9(1), 680–686.
30. Muruato AE, et al. A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation. Nat. Commun. 2020; 11(1), 1-6.
31. GeurtsvanKessel CH, et al. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat. Commun. 2020; 11(5), 1-5.
32. Guzman MG, et al. Dengue : a continuing global threat. Nat. Publ. Gr. 2010; 8(12), S7–S16.
33. Weaver SC, Lecuit M. Chikungunya virus and the global spread of a mosquito-borne disease. New England Journal of Medicine. 2015; 372(13), 1231–1239.
34. Long Q.-X, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 2020; 26(6), 845-848. doi:10.1038/s41591-020-0897-1
35. Lou B, et al. Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset. medRxiv 2020.03.23.20041707 (2020). doi:10.1101/2020.03.23.20041707
36. Wu F, et al. Neutralizing Antibody Responses to SARS-CoV-2 in a COVID-19 Recovered Patient Cohort and Their Implications. SSRN Electron. J. 2020.03.30.20047365 (2020). doi:10.1101/2020.03.30.20047365
37. Garcia-Basteiro AL, et al. Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital. Nature Communications. 2020;11(1), 1-9.
38. Padoan A, et al. IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study. Clin. Chim. Acta. 2020; 507(1), 164–166.
39. Yu H, et al. Distinct features of SARS-CoV-2-specific IgA response in COVID-19 patients. Eur. Respir. J. 2001526 (2020). doi:10.1183/13993003.01526-2020
40. Hu Q, et al. The Production and Clinical Implications of SARS-CoV-2 Antibodies. SSRN Electron. J. 2020.04.20.20065953 (2020). doi:10.1101/2020.04.20.20065953
41. Hanson KE, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. www.idsociety.org/COVID19guidelines/serology. (2020). Disponble en: www.idsociety.org/COVID19guidelines/serology.
42. Tan W, et al. Viral Kinetics and Antibody Responses in Patients with COVID-19. medRxiv 2020.03.24.20042382 (2020). doi:10.1101/2020.03.24.20042382
43. Huang J, et al. Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study. medRxiv (Cold Spring Harbor Laboratory Press, 2020). doi:10.1101/2020.04.22.20071258
44. Altmann DM, Douek DC, Boyton RJ. What policy makers need to know about COVID-19 protective immunity. The Lancet. 2020; 395(10236), 1527–1529.
45. Wang X, et al. Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients. Clin. Infect. Dis. 2020 71(10), 2688-2694. doi:10.1093/cid/ciaa721
46. Iwasaki A, Yang, Y. The potential danger of suboptimal antibody responses in COVID-19. Nat. Rev. Immunol. 2020; 20(6), 339-341. doi:10.1038/s41577-020-0321-6
47. Wu J, et al. SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19 Correspondence. medRxiv 2020.07.21.20159178 (2020). doi:10.1101/2020.07.21.20159178
48. To KK-W, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin. Infect. Dis. 2020. doi:10.1093/cid/ciaa1275
49. Ismail, A. ANNALS EXPRESS: Serological tests for Covid-19 antibodies: limitations must be recognised. Ann. Clin. Biochem. Int. J. Lab. Med. 2020;57(4),274-276. 000456322092705. 2020. doi:10.1177/0004563220927053
50. Salje H, et al. Estimating the burden of SARS-CoV-2 in France. Science. 2020; 369(6500), 208–211.
51. Guo L, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin. Infect. Dis. 2020; 71(1), 778–785.
52. Verdoni L, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020; 395(10239), 1771–1778.
53. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. Journal of Clinical Investigation. 2020; 130(4), 1545–1548.
54. Maiztegui J, Alba J, Fernandez, NJ. Efficacy of immune plasma in treatmen of Argentine haemorrhagic fever and association between tratment and a late neurological syndrome. Lancet. 1979; 54(1), 1216–1217. 1216–1217.
55. Bloch EM, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. Journal of Clinical Investigation. 2020; 130(6), 2757–2765.
56. Adarsh Bhimraj A, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. www.idsociety.org/COVID19guidelines/treatment. 2020. Disponible en: www.idsociety.org/COVID19guidelines.
57. Duan K, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. 202004168. 2020. doi:10.1073/pnas.2004168117
58. World Health Organization. Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases. 2020; 1–7.
59. Molina Arias, M. Lectura crítica en pequeñas dosis características de las pruebas diagnósticas. Pediatr. Aten. Primaria, 2013; 15(1), 169–173.
60. Amanat F, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. 2020; 26(1), 1033-1036..
61. CDC. Interim Guidelines for COVID-19 Antibody Testing | CDC. (2020). Diponible en: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html.