Diagnóstico de laboratorio de COVID-19
Palabras clave:
COVID-19, CORONAVIRUS, INFECCIONES POR CORONAVIRUS, DIAGNÓSTICO, TÉCNICAS DE LABORATORIO CLÍNICO
Resumen
Más de 500 test o pruebas diagnósticas para COVID-19 se están comercializando en el mercado mundial o se encuentran en avanzada fase de desarrollo. En esta situación, sin precedentes, es importante comprender el tipo de ensayos disponibles así como su rol en el proceso diagnóstico. El diagnóstico preciso es clave en el manejo de la pandemia. Esto permite la adecuada identificación de los casos, lo cual habilita las medidas posteriores de control: búsqueda de contactos y aislamiento. En esta revisión describiremos el fundamento y la utilidad de los diferentes tipos de pruebas para diagnóstico etiológico disponibles. También estableceremos las condiciones preanalíticas necesarias para su realización, la sensibilidad y especificidad clínicas, así como la correcta interpretación y emisión de los resultados.
Citas
(1) Foundation for Innovative New Diagnostics. SARS- COV-2 diagnostic pipeline. Disponible en: https://www.finddx.org/covid-19/pipeline/?avance=all&type=all&status=all§ion=show-all&action=default [Consulta: 18 abril 2020].
(2) Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20(6):656-7. doi: 10.1016/S1473- 3099(20)30232-2.
(3) Patel R, Babady E, Theel ES, Storch GA, Pinsky BA, St George K, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: value of diagnostic testing for SARS–CoV-2/ COVID-19. mBio 2020;11(2):e00722-20.
(4) Saah AJ, Hoover DR. “Sensitivity” and “specificity” reconsidered: the meaning of these terms in analytical and diagnostic settings. Ann Intern Med 1997; 126:91-4 doi: 10.7326/0003-4819-126-1-199701010-00026.
(5) Center for Diseases Control and Prevention. Information for laboratories about coronavirus (COVID-19). Disponible en: https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html [Consulta: 15 abril 2020].
(6) World Health Organization. Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases: interim guidance, 2 March 2020. Disponible en: https://apps.who.int/iris/handle/10665/331329 [Consulta: 15 abril 2020].
(7) Foundation for Innovative New Diagnostics. SARS- CoV-2 molecular assay evaluation: results. Disponible en: https://www.finddx.org/wp-content/uploads/2020/ 05/FIND_SARS-COV2_molecular-assay-evaluation-results_15May2020.pdf [Consulta: 27 mayo 2020].
(8) Grupo de expertos SEIMC para el análisis del diagnóstico microbiológico del COVID-19. Recomendaciones institucionales documento de posicionamiento de la SEIMC sobre el diagnóstico microbiólogo de COVID-19. SEIMC, 2000:7p. Disponible en: https://seimc.org/contenidos/documentoscientificos/recomendaciones/seimc-rc-2020-Posicionamiento_SEIMC_diagnostico_microbiologico_COVID19. pdf [Consulta: 27 mayo 2020].
(9) Organización Panamericana de la Salud. Directrices de laboratorio para la detección y el diagnóstico de la infección con el virus responsable de la COVID-19. Disponible en: https://www.paho.org/en/documents/laboratory-guidelines-detection-and-diagnosis-covid-19-virus-infection [Consulta: 22 abril 2020].
(10) UdelaR. Facultad de Medicina. Cátedra de Enfermedades Infecciosas. Actualización. Recomendaciones grupo interdisciplinario inter sociedades científicas e inter cátedras de Uruguay. Versión de 24 de marzo de 2020. Disponible en: http://www.infectologia.edu.uy/divulgacion-medica/novedades-y-avances/actualizacion-recomendaciones-intersociedades-y-catedras [Consulta: 22 abril 2020].
(11) Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20(4):411-2. doi: 10.1016/S1473-3099(20)30113-4.
(12) Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic transmission of SARS-CoV-2 – Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020; 69:411-5. doi: 10.15585/mmwr.mm6914e1.
(13) Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581:465-9. doi: 10.1038/s41586-020-2196-x.
(14) European Centre for Disease Prevention and Control. Questions and answers regarding laboratory topics on SARS-CoV-2. Disponible en: https://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/laboratory-support/questions [Consulta: 23 abril 2020].
(15) Marty FM, Chen K, Verrill KA; New England Journal of Medicine. Videos en Clinical Medicine. Performen medical procedures: how to obtain a nasopharyngeal swab specimen. 2020. Disponible en: https://www.youtube.com/watch ?v=1jVNeSnVSks [Consulta: 23 abril 2020].
(16) Center for Diseases Control and Prevention. Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Disponible en: https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html [Consulta: 15 abril 2020].
(17) Rodino KG, Espy MJ, Buckwalter SP, Walchak RC, Germer JJ, Fernholz E, et al. Evaluation of saline, phosphate-buffered saline and minimum essential medium as potential alternatives to viral transport media for SARS-CoV-2 testing. J Clin Microbiol May 2020; 58(6):e00590-20. doi: 10.1128/JCM.00590-20.
(18) Uruguay. Poder Ejecutivo. Decreto Nº 382/014 de 24/12/2014 artículo 1. Disponible en: https://www.impo. com.uy/bases/decretos-reglamento/382-2014/1 [Consulta: 15 abril 2020].
(19) World Health Organization. Laboratory biosafety guidance related to the novel coronavirus (2019-nCoV). Interim guidance 12 February 2020. Disponible en: https://www. who.int/docs/default-source/coronaviruse/laboratory-biosafety-novel-coronavirus-version-1-1.pdf?sfvrsn=912a9847_2 [Consulta: 15 abril 2020].
(20) van Kasteren PB, van der Veer B, van den Brink S, Wijsman L, de Jonge J, van den Brandt A, et al. Comparison of seven commercial RT-PCR diagnostic kits for COVID-19. J Clin Virology 2020; 128:104412. doi: 10.1016/j.jcv. 2020.104412.
(21) Moreno P, Moratorio GA, Iraola G, Fajardo A, Aldunate F, Pereira M, et al. An effective COVID-19 response in South America: the uruguayan conundrum. MedRxiv 2020.07.24.20161802. doi: 10.1101/2020.07.24.20161802.
(22) UdelaR; Institut Pasteur. COVID-19 RT-PCR Real TM Fast (HEX). Disponible en: http://www.atgen.com.uy/sitio/wp-content/uploads/2020/05/Inserto-71-v2-HEX.pdf [Consulta: 10 agosto 2020].
(23) 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; 20:565-74. doi: 10.1016/S1473-3099(20)30196-1.
(24) Cheng V, Wong S, Chen J, Yip C, Chuang V, Tsang O, et al. Escalating infection control response to the rapidly evolving epidemiology of the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol 2020; 41(5):493-8. doi: 10.1017/ ice.2020.58.
(25) Ramírez JD, Muñoz M, Hernández C, Florez C, Gomez S, Rico A, et al. Genetic diversity among SARS-CoV2 strains in South America may impact performance of molecular detection. Pathogens 2020; 9:580. doi: 10.3390/pathogens9070580.
(26) Artesi M, Bontems S, Göbbels P, Franckh M, Maes P, Boreux R, et al. A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilized in a commercial dual-target diagnostic assay. J Clin Microbiol 2020; 58(10):e01598-20. doi: 10.1128/JCM.01598-20.
(27) Hawkins R. Managing the pre- and post- analytical phases of the total testing process. Ann Lab Med 2012; 32:5-16. doi: 10.3343/alm.2012.32.1.5.
(28) Diao B, Wen K, Chen J, Liu Y, Yuan Z, Han C, et al. Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infections by detection of nucleocapsid protein. MedRxiv 2020.03.07. doi: 10.1101/2020.03.07.20032524.
(29) Lambert-Niclot S, Cuffel A, Le Pape S, Vauloup-Fellous C, Morand-Joubert L, Roque-Afonso AM, et al. Evaluation of a rapid diagnostic assay for detection of SARS-CoV-2 antigen in nasopharyngeal swabs. J Clin Microbiol 2020; 58(8):e00977-20. doi: 10.1128/JCM.00977-20.
(30) Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis 2020; 71(15): 778-85. doi: 10.1093/cid/ciaa310.
(31) Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv 2020.03.13.990226. doi: 10.1101/2020.03. 13.990226.
(32) 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; ciaa344. doi: 10.1093/cid/ciaa344.
(33) Food and Drug Administration. In vitro diagnostics EUAs. Emergency use authorization. Disponible en: https://www. fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations. [Consulta: 23 junio 2020].
(34) Foundation for Innovative New Diagnostics. SARS-CoV-2 diagnostics: performance data. Disponible en: https://www.finddx.org/covid-19/dx-data/ [Consulta: 27 mayo 2020].
(35) España. Ministerio de Sanidad. Instituto de Salud Carlos III. Interpretacioìn de las pruebas diagnoìsticas frente a SARS-CoV-2. 24 de abril de 2020. versioìn 2. Disponible en: https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/ alertasActual/nCovChina/documentos/INTERPRETACION_ DE_LAS_PRUEBAS.pdf. [Consulta: 23 junio 2020].
(2) Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20(6):656-7. doi: 10.1016/S1473- 3099(20)30232-2.
(3) Patel R, Babady E, Theel ES, Storch GA, Pinsky BA, St George K, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: value of diagnostic testing for SARS–CoV-2/ COVID-19. mBio 2020;11(2):e00722-20.
(4) Saah AJ, Hoover DR. “Sensitivity” and “specificity” reconsidered: the meaning of these terms in analytical and diagnostic settings. Ann Intern Med 1997; 126:91-4 doi: 10.7326/0003-4819-126-1-199701010-00026.
(5) Center for Diseases Control and Prevention. Information for laboratories about coronavirus (COVID-19). Disponible en: https://www.cdc.gov/coronavirus/2019-nCoV/lab/index.html [Consulta: 15 abril 2020].
(6) World Health Organization. Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases: interim guidance, 2 March 2020. Disponible en: https://apps.who.int/iris/handle/10665/331329 [Consulta: 15 abril 2020].
(7) Foundation for Innovative New Diagnostics. SARS- CoV-2 molecular assay evaluation: results. Disponible en: https://www.finddx.org/wp-content/uploads/2020/ 05/FIND_SARS-COV2_molecular-assay-evaluation-results_15May2020.pdf [Consulta: 27 mayo 2020].
(8) Grupo de expertos SEIMC para el análisis del diagnóstico microbiológico del COVID-19. Recomendaciones institucionales documento de posicionamiento de la SEIMC sobre el diagnóstico microbiólogo de COVID-19. SEIMC, 2000:7p. Disponible en: https://seimc.org/contenidos/documentoscientificos/recomendaciones/seimc-rc-2020-Posicionamiento_SEIMC_diagnostico_microbiologico_COVID19. pdf [Consulta: 27 mayo 2020].
(9) Organización Panamericana de la Salud. Directrices de laboratorio para la detección y el diagnóstico de la infección con el virus responsable de la COVID-19. Disponible en: https://www.paho.org/en/documents/laboratory-guidelines-detection-and-diagnosis-covid-19-virus-infection [Consulta: 22 abril 2020].
(10) UdelaR. Facultad de Medicina. Cátedra de Enfermedades Infecciosas. Actualización. Recomendaciones grupo interdisciplinario inter sociedades científicas e inter cátedras de Uruguay. Versión de 24 de marzo de 2020. Disponible en: http://www.infectologia.edu.uy/divulgacion-medica/novedades-y-avances/actualizacion-recomendaciones-intersociedades-y-catedras [Consulta: 22 abril 2020].
(11) Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20(4):411-2. doi: 10.1016/S1473-3099(20)30113-4.
(12) Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic transmission of SARS-CoV-2 – Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020; 69:411-5. doi: 10.15585/mmwr.mm6914e1.
(13) Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581:465-9. doi: 10.1038/s41586-020-2196-x.
(14) European Centre for Disease Prevention and Control. Questions and answers regarding laboratory topics on SARS-CoV-2. Disponible en: https://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/laboratory-support/questions [Consulta: 23 abril 2020].
(15) Marty FM, Chen K, Verrill KA; New England Journal of Medicine. Videos en Clinical Medicine. Performen medical procedures: how to obtain a nasopharyngeal swab specimen. 2020. Disponible en: https://www.youtube.com/watch ?v=1jVNeSnVSks [Consulta: 23 abril 2020].
(16) Center for Diseases Control and Prevention. Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Disponible en: https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html [Consulta: 15 abril 2020].
(17) Rodino KG, Espy MJ, Buckwalter SP, Walchak RC, Germer JJ, Fernholz E, et al. Evaluation of saline, phosphate-buffered saline and minimum essential medium as potential alternatives to viral transport media for SARS-CoV-2 testing. J Clin Microbiol May 2020; 58(6):e00590-20. doi: 10.1128/JCM.00590-20.
(18) Uruguay. Poder Ejecutivo. Decreto Nº 382/014 de 24/12/2014 artículo 1. Disponible en: https://www.impo. com.uy/bases/decretos-reglamento/382-2014/1 [Consulta: 15 abril 2020].
(19) World Health Organization. Laboratory biosafety guidance related to the novel coronavirus (2019-nCoV). Interim guidance 12 February 2020. Disponible en: https://www. who.int/docs/default-source/coronaviruse/laboratory-biosafety-novel-coronavirus-version-1-1.pdf?sfvrsn=912a9847_2 [Consulta: 15 abril 2020].
(20) van Kasteren PB, van der Veer B, van den Brink S, Wijsman L, de Jonge J, van den Brandt A, et al. Comparison of seven commercial RT-PCR diagnostic kits for COVID-19. J Clin Virology 2020; 128:104412. doi: 10.1016/j.jcv. 2020.104412.
(21) Moreno P, Moratorio GA, Iraola G, Fajardo A, Aldunate F, Pereira M, et al. An effective COVID-19 response in South America: the uruguayan conundrum. MedRxiv 2020.07.24.20161802. doi: 10.1101/2020.07.24.20161802.
(22) UdelaR; Institut Pasteur. COVID-19 RT-PCR Real TM Fast (HEX). Disponible en: http://www.atgen.com.uy/sitio/wp-content/uploads/2020/05/Inserto-71-v2-HEX.pdf [Consulta: 10 agosto 2020].
(23) 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; 20:565-74. doi: 10.1016/S1473-3099(20)30196-1.
(24) Cheng V, Wong S, Chen J, Yip C, Chuang V, Tsang O, et al. Escalating infection control response to the rapidly evolving epidemiology of the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol 2020; 41(5):493-8. doi: 10.1017/ ice.2020.58.
(25) Ramírez JD, Muñoz M, Hernández C, Florez C, Gomez S, Rico A, et al. Genetic diversity among SARS-CoV2 strains in South America may impact performance of molecular detection. Pathogens 2020; 9:580. doi: 10.3390/pathogens9070580.
(26) Artesi M, Bontems S, Göbbels P, Franckh M, Maes P, Boreux R, et al. A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilized in a commercial dual-target diagnostic assay. J Clin Microbiol 2020; 58(10):e01598-20. doi: 10.1128/JCM.01598-20.
(27) Hawkins R. Managing the pre- and post- analytical phases of the total testing process. Ann Lab Med 2012; 32:5-16. doi: 10.3343/alm.2012.32.1.5.
(28) Diao B, Wen K, Chen J, Liu Y, Yuan Z, Han C, et al. Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infections by detection of nucleocapsid protein. MedRxiv 2020.03.07. doi: 10.1101/2020.03.07.20032524.
(29) Lambert-Niclot S, Cuffel A, Le Pape S, Vauloup-Fellous C, Morand-Joubert L, Roque-Afonso AM, et al. Evaluation of a rapid diagnostic assay for detection of SARS-CoV-2 antigen in nasopharyngeal swabs. J Clin Microbiol 2020; 58(8):e00977-20. doi: 10.1128/JCM.00977-20.
(30) Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis 2020; 71(15): 778-85. doi: 10.1093/cid/ciaa310.
(31) Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv 2020.03.13.990226. doi: 10.1101/2020.03. 13.990226.
(32) 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; ciaa344. doi: 10.1093/cid/ciaa344.
(33) Food and Drug Administration. In vitro diagnostics EUAs. Emergency use authorization. Disponible en: https://www. fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations. [Consulta: 23 junio 2020].
(34) Foundation for Innovative New Diagnostics. SARS-CoV-2 diagnostics: performance data. Disponible en: https://www.finddx.org/covid-19/dx-data/ [Consulta: 27 mayo 2020].
(35) España. Ministerio de Sanidad. Instituto de Salud Carlos III. Interpretacioìn de las pruebas diagnoìsticas frente a SARS-CoV-2. 24 de abril de 2020. versioìn 2. Disponible en: https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/ alertasActual/nCovChina/documentos/INTERPRETACION_ DE_LAS_PRUEBAS.pdf. [Consulta: 23 junio 2020].
Publicado
2020-12-01
Cómo citar
1.
López P, Ballesté R, Seija V. Diagnóstico de laboratorio de COVID-19. Rev. Méd. Urug. [Internet]. 1 de diciembre de 2020 [citado 14 de noviembre de 2024];36(4):393-00. Disponible en: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/645
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