Discussion
Cutting off the route of transmission is an important preventive measure for infectious disease. However, it has been reported recently that asymptomatic carrier can lead to person-to-person transmission in community due to the neglect. This will also pose a huge challenge for COVID-19 prevention and control. Therefore, the proportion of asymptomatic infections needs to be determined timely through proper laboratory techniques.
There are two situations in asymptomatic patients with COVID-19: infected individuals with positive viral nucleic acid test results but no recognizable symptoms and signs after observation for 14 days, and asymptomatic infections within the incubation period. As shown here, the nucleic acid test results of the infected individuals could be positive, even without self-perceived or clinically recognizable symptoms and signs during sampling, however, clinical manifestations could appear later.
It was reported that a 20-year-old female asymptomatic patient infected the five other members of her family after returning to Anyang, Henan province of China in January 10, 2020 [6]. The five family members developed symptoms (fever and cough) and were diagnosed with COVID-19. Nevertheless, the asymptomatic patient remains free of clinical symptoms, and her C-reactive protein and chest CT examination were normal. With the emergence of increased cases from abroad, the asymptomatic SARS-CoV-2 populations have attracted more attention as a hidden source of infection. As of August 21, 2020, there are 353 asymptomatic infections under medical observation in China, including 248 imported cases [7].
Identifying asymptomatic infected populations early and accurately is essential for the epidemic prevention and control. Here, we provide evidence for screening infection in 26 asymptomatic individuals through dynamic analysis of IgM and IgG antibodies. It provides a laboratory basis for understanding the status of the immune system and the pattern of specific antibodies production. In this study, 33 asymptomatic cases with positive nucleic acid were screened, and 7 of them were converted to confirmed COVID-19 cases following their development of fever, cough, and chest CT imaging changes during the period of medical quarantine and observation, the remaining 26 remained asymptomatic. However, these 7 patients with COVID-19 did not receive continuous quantitative monitoring of serum antibody. So, it is impossible to compare and analyze the characteristics of antibody between asymptomatic and confirmed patients.
To further evaluate the production of SARS-CoV-2 specific antibodies in asymptomatic patients, blood specimens were collected regularly to detect the levels of serum SARS-CoV-2 specific IgM and IgG antibodies after nucleic acid converted to negative. The positive rate of IgM antibodies in asymptomatic individuals was significantly higher even when their nucleic acid converted to negative than that in healthy people. However, there was no significant difference in changes within 7 weeks after nucleic acid negative conversion (p<0.05). Our previous study showed that the positive rate of IgM in patients with COVID-19 was 75.9% [8]. These results suggest that IgM may be a useful target in screening the cases who previously infected by SARS-CoV-2 and healthy people. Furthermore, IgM in some asymptomatic individuals after nucleic acid convert to negative is not easy to degrade within 7 weeks.
According our study, the serum concentration of IgG in asymptomatic individuals after the nucleic acid converted to negative were in high level and increased with time in the 7 weeks we observed. The positive rate of serum IgG in asymptomatic group was 93.5% during 7 weeks after the nucleic acid turned to negative. While Long QX, et al[9] reported that the positive rate of serum IgG in patients with acute phase COVID-19 was 18.9%, while in convalescent-phase COVID-19 was 60.0%, patients with acute phase.
To date, studies have focused more on antibodies in patients with a confirmed diagnosis rather than changes in antibody levels in asymptomatic patients following the nucleic acid negative conversion. For instance, Fei Xiang at al. found that the sensitivity and specificity of IgM were 77.3% and 100%, respectively, and the sensitivity and specificity of IgG were 83.3% and 95.0%, respectively, during detection of antibodies in COVID-19 patients[10]. Our previous study found that the sensitivity of IgG (90.5%) was higher than that of IgM (75.9%), and the specificity of IgG (99.3%) was higher than that of IgM (94.0%) in COVID-19 patients [8]. Taken together, this indicates that the positive rate of IgM in asymptomatic patients after nucleic acid negative conversion is significantly lower than that in confirmed patients, while IgG remains at the same level as that of confirmed patients. Unfortunately, this study was unable to obtain serum specimens from asymptomatic patients when their nucleic acid was positive, and thus it was not possible to compare changes in antibody levels between nucleic acid positive and negative.
In conclusion, nucleic acid testing, though time consuming and susceptible to sampling errors, is recommended to be the main basis for the diagnosis of asymptomatic patients. Antibody detection holds great value in the diagnosis and identification of asymptomatic patients as it is fast, convenient, and the sampling is easily standardized.