ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off...

Full description

Saved in:
Bibliographic Details
Main Authors: Tao Suo, Xinjin Liu, Jiangpeng Feng, Ming Guo, Wenjia Hu, Dong Guo, Hafiz Ullah, Yang Yang, Qiuhan Zhang, Xin Wang, Muhanmmad Sajid, Zhixiang Huang, Liping Deng, Tielong Chen, Fang Liu, Ke Xu, Yuan Liu, Qi Zhang, Yingle Liu, Yong Xiong, Guozhong Chen, Ke Lan, Yu Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1772678
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849731452044836864
author Tao Suo
Xinjin Liu
Jiangpeng Feng
Ming Guo
Wenjia Hu
Dong Guo
Hafiz Ullah
Yang Yang
Qiuhan Zhang
Xin Wang
Muhanmmad Sajid
Zhixiang Huang
Liping Deng
Tielong Chen
Fang Liu
Ke Xu
Yuan Liu
Qi Zhang
Yingle Liu
Yong Xiong
Guozhong Chen
Ke Lan
Yu Chen
author_facet Tao Suo
Xinjin Liu
Jiangpeng Feng
Ming Guo
Wenjia Hu
Dong Guo
Hafiz Ullah
Yang Yang
Qiuhan Zhang
Xin Wang
Muhanmmad Sajid
Zhixiang Huang
Liping Deng
Tielong Chen
Fang Liu
Ke Xu
Yuan Liu
Qi Zhang
Yingle Liu
Yong Xiong
Guozhong Chen
Ke Lan
Yu Chen
author_sort Tao Suo
collection DOAJ
description Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27–55%), 100% (95% CI: 54–100%), 100%, 16% (95% CI: 13–19%), 0.6 (95% CI: 0.48–0.75) and 47% (95% CI: 33–60%) for RT-PCR to 94% (95% CI: 83–99%), 100% (95% CI: 48–100%), 100%, 63% (95% CI: 36–83%), 0.06 (95% CI: 0.02–0.18), and 95% (95% CI: 84–99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5–12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.
format Article
id doaj-art-94a5cb75fbe44dc9b853b6b3b0148a9c
institution DOAJ
issn 2222-1751
language English
publishDate 2020-01-01
publisher Taylor & Francis Group
record_format Article
series Emerging Microbes and Infections
spelling doaj-art-94a5cb75fbe44dc9b853b6b3b0148a9c2025-08-20T03:08:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911259126810.1080/22221751.2020.1772678ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimensTao Suo0Xinjin Liu1Jiangpeng Feng2Ming Guo3Wenjia Hu4Dong Guo5Hafiz Ullah6Yang Yang7Qiuhan Zhang8Xin Wang9Muhanmmad Sajid10Zhixiang Huang11Liping Deng12Tielong Chen13Fang Liu14Ke Xu15Yuan Liu16Qi Zhang17Yingle Liu18Yong Xiong19Guozhong Chen20Ke Lan21Yu Chen22State Key Laboratory of Virology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaState Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaQuantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27–55%), 100% (95% CI: 54–100%), 100%, 16% (95% CI: 13–19%), 0.6 (95% CI: 0.48–0.75) and 47% (95% CI: 33–60%) for RT-PCR to 94% (95% CI: 83–99%), 100% (95% CI: 48–100%), 100%, 63% (95% CI: 36–83%), 0.06 (95% CI: 0.02–0.18), and 95% (95% CI: 84–99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5–12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.https://www.tandfonline.com/doi/10.1080/22221751.2020.1772678SARS-CoV-2droplet digital PCRRT-PCRclinical detectionfalse negative
spellingShingle Tao Suo
Xinjin Liu
Jiangpeng Feng
Ming Guo
Wenjia Hu
Dong Guo
Hafiz Ullah
Yang Yang
Qiuhan Zhang
Xin Wang
Muhanmmad Sajid
Zhixiang Huang
Liping Deng
Tielong Chen
Fang Liu
Ke Xu
Yuan Liu
Qi Zhang
Yingle Liu
Yong Xiong
Guozhong Chen
Ke Lan
Yu Chen
ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
Emerging Microbes and Infections
SARS-CoV-2
droplet digital PCR
RT-PCR
clinical detection
false negative
title ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
title_full ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
title_fullStr ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
title_full_unstemmed ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
title_short ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens
title_sort ddpcr a more accurate tool for sars cov 2 detection in low viral load specimens
topic SARS-CoV-2
droplet digital PCR
RT-PCR
clinical detection
false negative
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1772678
work_keys_str_mv AT taosuo ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT xinjinliu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT jiangpengfeng ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT mingguo ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT wenjiahu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT dongguo ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT hafizullah ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT yangyang ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT qiuhanzhang ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT xinwang ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT muhanmmadsajid ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT zhixianghuang ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT lipingdeng ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT tielongchen ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT fangliu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT kexu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT yuanliu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT qizhang ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT yingleliu ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT yongxiong ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT guozhongchen ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT kelan ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens
AT yuchen ddpcramoreaccuratetoolforsarscov2detectioninlowviralloadspecimens