Clinical significance of IgM and IgG test for diagnosis of highly suspected COVID-19 infection

Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We suggest a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.


Introduction
COVID-19 which was discovered in Wuhan due to pneumonia virus cases in 2019 [1], and was named by the World Health Organization on January 12, 2020. Coronaviruses are a large family of viruses that are known to cause colds and more serious diseases [2]. COVID-19 is a novel coronavirus strain that has never been found in humans before. Common signs of a person infected with COVID-19 include respiratory symptoms, fever, cough, shortness of breath, and dyspnea.
In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death. There is currently no specific treatment for diseases caused by COVID-19 [3].
However, many symptoms can be managed, so they need to be shown that cases can be traced to close contact with confirmed cases [4,5].
According to the sixth edition of the diagnostic criteria, the COVID-19 cases are divided into two categories: "suspected cases" and "confirmed cases". As of 24:00 on February 25, a total of 77,789 confirmed cases have been reported in China, 27,836 cases have All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02. 28

Patients
This is a retrospective study which was approved by the Ethics Committee of Shenzhen Hospital, Southern Medical University (NYSZYYEC20200009). The data were anonymous, so the requirement for informed consent was therefore waived. Total 57 suspected COVID-19 infection patients were enrolled in our study All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (2) has a contact history with people infected with COVID-19 (positive nucleic acid test) within 14 days before onset; (3) has a contact history with patients from Wuhan and surrounding areas, or has a contact history with patients who has fever or respiratory symptoms from communities with COVID-19; (4) Cluster onset.

Laboratory Examination
Blood routine and hs-CRP were detected by Mindray  author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28.

Data analysis
Statistical analyses were performed with the Statistical Analysis System software SPSS 19.0, and data are presented as Median (25% All rights reserved. No reuse allowed without permission.
author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28.20029025 doi: medRxiv preprint percentile, 75% percentile). With nonparametric test and two-sided χ 2 test, we compared the differences between the two groups, and the P-value <0.05, which will be considered statistically significant.

IgM and IgG single detection for COVID-19
According to the nucleic acid test results, we performed IgM and IgG detection by the Diagreat company. As shown in Figure 1A, among the 33 All rights reserved. No reuse allowed without permission.
author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28.20029025 doi: medRxiv preprint patients with COVID-19 nucleic acid negative results, the IgM fluorescence intensity (Flu) of 20 patients was more than 0.88, the positive rate was 60.61%. As shown in Figure 1B, the IgG Flu of 15 patients was more than 1.02, the positive rate was 45.45%. As shown in Figure 2A, among the 24 patients with COVID-19 nucleic acid positive results, the IgM Flu of 19 patients was more than 0.88, the positive rate was 79.17%. As shown in Figure 2B, the IgG Flu of 16 patients was more than 1.02, the positive rate was 66.67%.

Combination of IgM and IgG detection for COVID-19
As shown in Figure 3A author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28.20029025 doi: medRxiv preprint detection for 24 patients with COVID-19 negative nucleic acid test was 87.50%. Compared with the nucleic acid positive test, IgM and IgG single detection, the combination of IgM and IgG also showed significantly increased (P<0.01).

Discussion
In our study, the positive rate of COVID-19 nucleic acid in the 57 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28. In the lower of both lungs, there were large fuzzy shadows and GGO, some slightly fan-shaped distribution. Third, because of the laboratory pollution, the positive results may be also false positive. As shown in Figure 7B, the nucleic acid detection result of Patient ID 19 was positive, but the IgM and IgG were negative results, according to the CT results, All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the only causes lung injury, but also causes multiple organs such as the liver, heart muscle, and kidney damage. Therefore, "inflammatory storm" is All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. There are still some limitations in our study. First, the relatively small sample size, difference of IgM and IgG antigen binding site, difference of COVID-19 nucleic acid design, it may result in the bias of results. Second, because of the different time that from a patient who were firstly exposed to the virus to the detection, the detection positive rate of IgM and IgG may be affected. Earlier and different times should be performed to All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.28.20029025 doi: medRxiv preprint validate the detection value of IgM and IgG. Third, the detection value of IgM and IgG should be followed up in the future study.
In summary, compared with the nucleic acid detection, the IgM and IgG may provide a quick, simple and accurate aided detection method for suspected COVID-19 patients. We should combine the nucleic acid, IgM, IgG, CT scan and clinical characteristics results together for the diagnosis of COVID-19. In the lower of both lungs, there were large fuzzy shadows and GGO, some slightly fan-shaped distribution. B: Patient ID 19, the nucleic acid detection result was positive, but the IgM and IgG results were negative, no obvious lesion was found in both lungs. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.