Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis

Original Article: Zhengtu Li , Yongxiang Yi , Xiaomei Luo , Nian Xiong , Yang Liu , Shaoqiang Li , Ruilin Sun , Yanqun Wang , Bicheng Hu , Wei Chen , Yongchen Zhang , Jing Wang , Baofu Huang , Ye Lin , Jiasheng Yang , Wensheng Cai , Xuefeng Wang , Jing Cheng , Zhiqiang Chen , Kangjun Sun , Weimin Pan , Zhifei Zhan , Liyan Chen , Feng Ye, “Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis”, Journal of Medical Virology.

Author of summary: Gianmarco Taraschi; Reviewer: Valeria Guidolin

Original Article Published on February 27th, 2020

A new rapid and simple immunoassay was developed and tested for SARS-CoV2 (IgM-IgG combined). The sensitivity and specificity reported are respectively 88.66% and 90.63% for venous blood samples. A small number of subjects were also tested by using fingerstick blood samples, leading to a promising application of this test. Further validation and testing of cross-reactivity with other coronaviruses and flu viruses are necessary.

Starting from the appearance of the new SARS-CoV2 in December 2019 in China, the virus has been spreading in the whole world becoming pandemic. One dramatic issue is to be able to distinguish patients affected by COVID-19 from healthy subjects. Indeed, symptoms are non-specific (e.g. flu-like) and the diagnosis is based upon Real Time PCR (RT-PCR) assays, which are limited in some aspects: 1) time consuming; 2) certified laboratories required; 3) possible false negatives. The goal of the study was to develop a rapid, easy, sensitive and specific test to mitigate the virus transmission. On the basis of the data collected on SARS-CoV1 e MERS-CoV, authors hypothesize that the detection of specific antibodies related to SARS-CoV2 may be useful to confirm the exposure to the virus and to differentiate a recent exposure (IgM) from a older one (IgG).

The authors collected data from 525 patients: 397 being positive and 128 being negative to RT-PCR, from 8 hospitals in China. The kit is capable to detect both IgM and IgG and it is an immunochromatographic assay. Three lines are present on the strip: control, IgG and IgM (respectively in opposite order of the sample flow). The antigen recognized is a surface antigen of SARS-CoV2.

Out of 397 blood samples of SARS-CoV2 positive, 352 were confirmed positive with the new test. The calculated sensitivity is 88,66%. Out of 128 blood samples negative for SARS-CoV2, 12 resulted positive, leading to a specificity of a 90.63%. In 64.4% of positive subjects, the test was positive for both IgG and IgM.

The authors tested sensitivity and specificity of the test for both venous and fingerstick blood from 7 positive patients and 3 healthy volunteers. From all subjects, both venous and fingerstick blood was collected. Out of 7 COVID-19 positive patients, 3 were positive for only IgM and 4 for both IgM and IgG. All healthy volunteers were negative. 100% consistency was observed with the fingerstick samples, leading to the conclusion that this kit might be used as point-of-care test.

Even if encouraging results were observed with the kit, the authors highlight the possible presence of false negatives and false positives. Respectively, the first can arise from an antibody concentration lower than the limit of detection or from the individual response to the virus.  Furthermore, IgM decreases and disappears in two weeks. Therefore, at the time of the test, IgM can already be under the limit of detection. False positive may arise from the interference of other virus antigens, even though the authors reassure that the recombinant antigen is SARS-CoV2 specific (validation is missing).

Pros: the kit is simple, rapid and can be used in and out from the hospital. Fingerstick blood can be used; it can be useful to identify asymptomatic subjects having SARS-CoV2 and for therapy surveillance.

Cons: the test cannot confirm the actual presence of the virus; chance of cross-reactivity with other viruses

Conclusions: promising test, further validations are needed.

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