Estandarización y validación de una prueba molecular RT-LAMP in house para el diagnóstico de SARS-CoV-2

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Abstract

Objetivos: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. Materiales y métodos: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. Resultados: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/μL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 μL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83–0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). Conclusiones: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.

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  1. SciScore for 10.1101/2020.10.14.20212977: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: 2.1. ETHICAL CONSIDERATIONS: The laboratory standardization did not need to be sent for evaluation by the Ethics Committee since it is included in the action plan of INS-Peru.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We know that this point was a limitation of our study because this analysis should be done in vitro using clinical samples. Furthermore, the INS does not have positive clinical samples for other HCoV. Due to the need to quickly evaluate the performance of this diagnostic method and finally start transferring this technology to the points of attention, the alternative of verifying the occurrence of cross reaction measured by in silico analysis was the most appropriate and scientifically feasible at the moment. The perfect identity in the region of primers alignment F3 and B3 with all available SARS-CoV-2 Peruvian strains (figure 2, panels C and D) also indicated specific detection and almost none probability of false negative results due primers specificity. The robustness evaluation of this RT-LAMP protocol considered variables as primers concentration and final volume of reaction. This strategy focused the fact of the reactions will be performed by people that does not present routine contact with molecular biology techniques. Since the reactions performance was not compromised using half of primers concentrations and eighty percent of final volume of reaction, technical errors that may be made during small volume pipetting. The RT-LAMP presented a high sensitivity and specificity in the both steps of quality verification (87.4% and 98.7%, 88.1% and 98.8%, available in table 8 obtained by results presented in tables 6 and 7 in the laboratory standardization and in the clinic...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.