A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients

Liu, Lei; Liu, Wanbing; Zheng, Yaqiong; Jiang, Xiaojing; Kou, Guomei; Ding, Jinya; Wang, Qiongshu; Huang, Qingchun; Ding, Yinjuan; Ni, Wenxu; Wu, Wanlei; Tang, Shi; Tan, Li; Hu, Zhenhong; Xu, Weitian; Zhang, Yong; Zhang, Bo; Tang, Zhongzhi; Zhang, Xinhua; Li, Honghua; Rao, Zhiguo; Jiang, Hui; Ren, Xingfeng; Wang, Shengdian; Zheng, Shangen

doi:10.1101/2020.03.06.20031856

Cited by 52 publications

(60 citation statements)

References 21 publications

(31 reference statements)

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“…Our kits have much higher accuracy than RT-qPCR (sensitivity less than 70%) for detecting viral RNA [9][10][11][12][13] , and published immune-assays such as " flow immunoassay" and ELISA in earlier studies 10-12, 17-21, 23, 24 . When we combined RBD-specific IgA and IgG kits together, the sensitivity, specificity and overall agreement elevate to 99• 1%, 100%, and 99• 7%, respectively (table 1).…”

Section: Our Serological Kits Have Overall Good Performancementioning

confidence: 99%

“…Both challenges result in a sensitivity below 70%. [9][10][11][12][13] Therefore, there is an urgent need for more reliable and rapid diagnostic methods to screen SARS-CoV-2 infected people including those who do not have overt symptoms. A serological test of virus-induced antibody production has unique advantages in clinical diagnostics, especially for identifying people who acquired immunity against pathogens without noticeable symptoms.…”

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confidence: 99%

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COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by chemiluminescence immunoanalysis

2020

Preprint

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Highlights 42  Developed a highly quantitative and sensitive serologic immunoassay for SARS-CoV-2-specific 43 IgA, IgM and IgG in COVID-19 patients. 44  Showed the inclusion of IgA to the conventional IgM + IgG in a serological test improves the 45 performance. 46  Revealed the kinetics of three antibody isotypes in COVID-19 patients. 47  Observed that serum IgA level positively correlated with COVID-19 disease severity. 48 49 Abstract 50 Background 51 The current pandemic of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has52 caused a great loss in lives and economy. Detecting viral RNAs on nasopharyngeal and throat swabs is 53 the standard approach for SARS-CoV-2 diagnosis with variable success. Currently, there are only a few 54 studies describing the serological diagnostic methods that involve the detection of SARS-CoV-2-specific 55 IgM and IgG. Here, we aimed to develop a more quantitative and sensitive serological test for COVID-56 19 diagnosis, monitoring and clinical investigation, based on the detection of antigen-specific IgA as 57 well as IgM and IgG in blood in response to SARS-CoV-2 infection. 58 59 Methods 60 In this investigation, we report the development of a set of validated diagnostic kits for detecting serum 61 IgA, IgM, and IgG specific to SARS-CoV-2 nucleocapsid protein (NP) and receptor-binding domain 62 (RBD) of the spike protein by chemi-luminescence immuno-analysis. The kits were tested with a cohort 63 of 216 sera from 87 laboratory-confirmed COVID-19 patients, and 483 sera from SARS-CoV-2 negative 64 or healthy individuals as negative controls. A standard receiver operating characteristic (ROC) analysis 65 was conducted to evaluate the diagnostic accuracy. Using the kits, serum levels of IgA, IgM, and IgG 66 were analyzed, in response to SARS-CoV-2 infection and COVID-19 pathogenesis. 68 Findings 69The diagnostic kits based on the RBD antigen outperformed those based on the NP. RBD-specific IgA, 70IgM, and IgG detection kits showed sensitivities of 98· 6%, 96· 8%, and 96· 8%, and specificities of 98· 1%, 7192· 3%, and 99· 8%, respectively. In addition, using purified RBD-specific immunoglobulins from a 72 serum pool of COVID-19 patients as standards, the serum concentrations of RBD-specific IgA, IgM, and 73 IgG proteins were determined. The concentrations varied widely among different patients. Median 74 concentration of IgA and IgM reached peaks at 16-20 days after illness onset at 8· 84 μg/mL and 7· 25 75 μg/mL, respectively, while median concentration of IgG peaked during 21-25 days after illness onset at 76 16· 47 μg/mL. Furthermore, the serum IgA level positively correlates with COVID-19 severity. 77 78 Interpretation 79

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Section: Our Serological Kits Have Overall Good Performancementioning

confidence: 99%

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confidence: 99%

COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by chemiluminescence immunoanalysis

2020

Preprint

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“…Many serological enzyme-linked immunosorbent assays (ELISA) have been recently developed to detect anti-SARS-CoV-2 antibodies. However, these assays have four important limitations [4][5][6][7][8][9][10][11][12][13][14][15] . First, they lack the ability to detect antibodies at early stages of infection.…”

Section: Mainmentioning

confidence: 99%

Ultra-Sensitive High-Resolution Profiling of Anti-SARS-CoV-2 Antibodies for Detecting Early Seroconversion in COVID-19 Patients

Norman

Gilboa

Ogata

et al. 2020

Preprint

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The COVID-19 pandemic continues to infect millions of people worldwide. In order to curb its spread and reduce morbidity and mortality, it is essential to develop sensitive and quantitative methods that identify infected individuals and enable accurate population-wide screening of both past and present infection. Here we show that Single Molecule Array assays detect seroconversion in COVID-19 patients as soon as one day after symptom onset using less than a microliter of blood. This multiplexed assay format allows us to quantitate IgG, IgM and IgA immunoglobulins against four SARS-CoV-2 targets, thereby interrogating 12 antibody isotype-viral protein interactions to give a high resolution profile of the immune response. Using a cohort of samples collected prior to the outbreak as well as samples collected during the pandemic, we demonstrate a sensitivity of 86% and a specificity of 100% during the first week of infection, and 100% sensitivity and specificity thereafter. This assay should become the gold standard for COVID19 serological profiling and will be a valuable tool for answering important questions about the heterogeneity of clinical presentation seen in the ongoing pandemic.

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“…It is evident that the infection may be effectively reduced and eventually controlled with swift and large-scale testing for early diagnostics [3][4][5][6] . Current testing methods include PCR nucleic acid detection with either thermal cycling 7,8 or isothermal amplification [9][10][11] , serological IgM/IgG antibody testing 12 as well as viral protein detections 13 in nasopharyngeal swap. The PCR based nucleic acid testing is very sensitive and accurate in early infection diagnostics but it generally requires multiple and lengthy processes including virus lysis, RNA extraction, reverse transcription and amplification and is prone to sample contamination 14,15 .…”

Section: Introductionmentioning

confidence: 99%

One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device

Huang

Ding

Zhou

et al. 2020

Preprint

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The spread of SARS-CoV-2 virus in the ongoing global pandemics has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemics. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples.Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. We demonstrate that we can detect as few as 30 virus particles in one step within 15 minutes and can quantify the virus concentration linearly in the range of 10 3 vp/ml to 10 6 vp/ml. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.

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A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients

Abstract: 30Background The outbreak of the recently emerged novel corona virus disease 2019

Cited by 52 publications

References 21 publications

COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by chemiluminescence immunoanalysis

COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by chemiluminescence immunoanalysis

Ultra-Sensitive High-Resolution Profiling of Anti-SARS-CoV-2 Antibodies for Detecting Early Seroconversion in COVID-19 Patients

One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device

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