Comparison of real-time and droplet digital PCR to detect and quantify SARS-CoV-2 RNA in plasma.


Journal

European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331

Informations de publication

Date de publication:
Jun 2021
Historique:
revised: 13 01 2021
received: 22 12 2020
accepted: 25 01 2021
pubmed: 30 1 2021
medline: 16 6 2021
entrez: 29 1 2021
Statut: ppublish

Résumé

The presence of SARS-CoV-2 RNA in plasma has been linked to disease severity and mortality. We compared RT-qPCR to droplet digital PCR (ddPCR) to detect SARS-CoV-2 RNA in plasma from COVID-19 patients (mild, moderate, and critical disease). The presence/concentration of SARS-CoV-2 RNA in plasma was compared in three groups of COVID-19 patients (30 outpatients, 30 ward patients and 30 ICU patients) using both RT-qPCR and ddPCR. Plasma was obtained in the first 24h following admission, and RNA was extracted using eMAG. ddPCR was performed using Bio-Rad SARS-CoV-2 detection kit, and RT-qPCR was performed using GeneFinder™ COVID-19 Plus RealAmp Kit. Statistical analysis was performed using Statistical Package for the Social Science. SARS-CoV-2 RNA was detected, using ddPCR and RT-qPCR, in 91% and 87% of ICU patients, 27% and 23% of ward patients and 3% and 3% of outpatients. The concordance of the results obtained by both methods was excellent (Cohen's kappa index = 0.953). RT-qPCR was able to detect 34/36 (94.4%) patients positive for viral RNA in plasma by ddPCR. Viral RNA load was higher in ICU patients compared with the other groups (P < .001), by both ddPCR and RT-qPCR. AUC analysis revealed Ct values (RT-qPCR) and viral RNA load values (ddPCR) can similarly differentiate between patients admitted to wards and to the ICU (AUC of 0.90 and 0.89, respectively). Both methods yielded similar prevalence of RNAemia between groups, with ICU patients showing the highest (>85%). RT-qPCR was as useful as ddPCR to detect and quantify SARS-CoV-2 RNAemia in plasma.

Sections du résumé

BACKGROUND BACKGROUND
The presence of SARS-CoV-2 RNA in plasma has been linked to disease severity and mortality. We compared RT-qPCR to droplet digital PCR (ddPCR) to detect SARS-CoV-2 RNA in plasma from COVID-19 patients (mild, moderate, and critical disease).
METHODS METHODS
The presence/concentration of SARS-CoV-2 RNA in plasma was compared in three groups of COVID-19 patients (30 outpatients, 30 ward patients and 30 ICU patients) using both RT-qPCR and ddPCR. Plasma was obtained in the first 24h following admission, and RNA was extracted using eMAG. ddPCR was performed using Bio-Rad SARS-CoV-2 detection kit, and RT-qPCR was performed using GeneFinder™ COVID-19 Plus RealAmp Kit. Statistical analysis was performed using Statistical Package for the Social Science.
RESULTS RESULTS
SARS-CoV-2 RNA was detected, using ddPCR and RT-qPCR, in 91% and 87% of ICU patients, 27% and 23% of ward patients and 3% and 3% of outpatients. The concordance of the results obtained by both methods was excellent (Cohen's kappa index = 0.953). RT-qPCR was able to detect 34/36 (94.4%) patients positive for viral RNA in plasma by ddPCR. Viral RNA load was higher in ICU patients compared with the other groups (P < .001), by both ddPCR and RT-qPCR. AUC analysis revealed Ct values (RT-qPCR) and viral RNA load values (ddPCR) can similarly differentiate between patients admitted to wards and to the ICU (AUC of 0.90 and 0.89, respectively).
CONCLUSION CONCLUSIONS
Both methods yielded similar prevalence of RNAemia between groups, with ICU patients showing the highest (>85%). RT-qPCR was as useful as ddPCR to detect and quantify SARS-CoV-2 RNAemia in plasma.

Identifiants

pubmed: 33512013
doi: 10.1111/eci.13501
pmc: PMC7995030
doi:

Substances chimiques

RNA, Viral 0

Types de publication

Comparative Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13501

Subventions

Organisme : European Society of Clinical Microbiology and Infectious Diseases
ID : Research Grant 2020 APT
Organisme : CIHR
ID : OV2 - 170357
Pays : Canada
Organisme : Instituto de Salud Carlos III
ID : CD018/0123
Organisme : Instituto de Salud Carlos III
ID : CIBERES 06/06/0028
Organisme : Instituto de Salud Carlos III
ID : COV20/00110
Organisme : CIHR
ID : OV2 - 170357
Pays : Canada

Informations de copyright

© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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Auteurs

Ana P Tedim (AP)

Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Hospital Universitario Río Hortega, Valladolid, Spain.

Raquel Almansa (R)

Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Hospital Universitario Río Hortega, Valladolid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.

Marta Domínguez-Gil (M)

Microbiology Service, Hospital Universitario Rio Hortega, Valladolid, Spain.

Milagros González-Rivera (M)

Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Dariela Micheloud (D)

Emergency Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Pablo Ryan (P)

Hospital Universitario Infanta Leonor, Madrid, Spain.

Raúl Méndez (R)

Pulmonology Service, Hospital Universitario y Politécnico de La Fe, Avinguda de Fernando Abril Martorell, Spain.

Natalia Blanca-López (N)

Hospital Universitario Infanta Leonor, Madrid, Spain.

Felipe Pérez-García (F)

Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias, Madrid, Spain.

Elena Bustamante (E)

Intensive Care Unit, Hospital Clínico Universitario de Valladolid. Av. Ramón y Cajal, Valladolid, Spain.

José Manuel Gómez (JM)

Intensive Care Unit. Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Cristina Doncel (C)

Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Hospital Universitario Río Hortega, Valladolid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.

Wysali Trapiello (W)

Clinical Analysis Service. Hospital, Clínico Universitario de Valladolid, Av. Ramón y Cajal, Valladolid, Spain.

Alyson A Kelvin (AA)

Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology CCfV, Dalhousie University, Halifax, Nova Scotia, Canada.
Laboratory of Immunity, Shantou University Medical College, Jinping, Shantou, China.

Ryan Booth (R)

Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology CCfV, Dalhousie University, Halifax, Nova Scotia, Canada.
Laboratory of Immunity, Shantou University Medical College, Jinping, Shantou, China.

Ali Toloue Ostadgavahi (AT)

Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology CCfV, Dalhousie University, Halifax, Nova Scotia, Canada.
Laboratory of Immunity, Shantou University Medical College, Jinping, Shantou, China.

Ruth Oneizat (R)

Microbiology Service, Hospital Universitario Rio Hortega, Valladolid, Spain.

Carolina Puertas (C)

Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Ferrán Barbé (F)

Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.
Respiratory Department, Institut Ricerca Biomedica de Lleida, Av. Alcalde Rovira Roure, Lleida, Spain.

Ricard Ferrer (R)

Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.
Intensive Care Department, SODIR Research Group, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca, Barcelona, Spain.

Rosario Menéndez (R)

Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.
Pulmonology Service, Hospital Universitario y Politécnico de La Fe, Avinguda de Fernando Abril Martorell, Spain.

Jesús F Bermejo-Martin (JF)

Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Hospital Universitario Río Hortega, Valladolid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.

José María Eiros (JM)

Microbiology Service, Hospital Universitario Rio Hortega, Valladolid, Spain.

David J Kelvin (DJ)

Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology CCfV, Dalhousie University, Halifax, Nova Scotia, Canada.
Laboratory of Immunity, Shantou University Medical College, Jinping, Shantou, China.

Antoni Torres (A)

Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, Madrid, Spain.
Department of Pulmonology, Institut D investigacions August Pi I Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Universidad de Barcelona, Barcelona, Spain.

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