Antibody responses of the first wave of survivors infected with SARS-CoV-2 1 year ago.

To The Editor,

As of 6:41 p.m. CEST, August 16, 2021, there have been 207 173 086 confirmed cases of coronavirus disease (COVID‐19), inclu ding 4 361 996 deaths worldwide. Antibody response is presumed to associate with host resistance to viral diseases and can protect against reinfection. , In view of the emergency and threat caused by the COVID‐19 outbreak, it is urgent to understand the host antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). So far, the short‐term changes of antibody responses in COVID‐19 patients have been reported in many studies. , However, little is known about long‐term changes and the duration of antibody responses in COVID‐19 patients. This information has major implications for understanding the duration of protective immunity from reinfection, vaccine efficacy, and herd immunity. This study focused on the antibody levels of people who were infected with SARS‐CoV‐2 1 year ago.

The study was conducted based on individuals who were infected with SARS‐CoV‐2 from January 12, 2020, and May 5, 2020, in Wuhan, China. According to the Protocol on Prevention and Control of Novel Coronavirus Pneumonia released by the Chinese Health Commission, asymptomatic individuals were defined as those with etiological detection of SARS‐CoV‐2 in respiratory specimens but had no clinical symptoms. A cohort of 67 individuals were enrolled, with 54 symptomatic cases and 13 asymptomatic cases. The median time from infection to serum sampling point was 357 days (interquartile range [IQR], 351–362 days). We collected blood samples from each participant for SARS‐CoV‐2‐specific serological tests. SARS‐CoV‐2 IgG, IgM, and neutralization antibodies were detected with a chemiluminescent immunoassay (YHLO Biotech) in human serum or plasma. Results of 10 AU/ml or higher were positive and results of less than 10 AU/ml were negative according to the manufacturer's recommendation. Furthermore, we divided the patients into a symptomatic group and an asymptomatic group and compared the levels of IgG, IgM, and neutralization antibodies between the two groups. All consecutive data were expressed as the median and IQR or the means ± SD and categorical data were expressed as the count (%) with Clopper–Pearson 95% confidence interval (CI). The data were analyzed by the corrected χ 2 test and independent t‐test. A p value less than 0.05 was considered significant.

Among the 67 participants infected with SARS‐CoV‐2, a total of 17 cases were males and 50 were females (Table 1). The median age was 35 years (IQR: 29–46 years). The positive rates of IgG, IgM, and neutralizing antibodies were 79.1% (95% CI: 67.4%–88.1%), 22.4% (95% CI: 13.1%–34.2%), and 67.2% (95% CI: 54.6%–78.2%), respectively. There was no significant difference in age (t = 1.825, p = 0.073) between the two groups. Symptomatic patients had significantly higher positivity for neutralizing antibodies (74.1%) compared to asymptomatic patients (38.5%), while no statistical significance for IgG and IgM (Table 2).

Table 1

The characteristics and antibody levels of serology of the study population

	All participants median and interquartile range	Symptomatic group median and interquartile range	Asymptomatic group median and interquartile range
Male/female	17/50	17/37	0/13
Age	35 (29–46)	36 (31–47)	32 (28–37)
IgG+	43.41 (10.90–76.17)	44.13 (13.1–85.30)	23.33 (5.52–55.20)
IgM+	2.72 (1.15–7.51)	2.91 (1.32–8.29)	1.25 (0.54–7.68)
Neutralization antibodies+	14.68 (6.99–29.17)	15.58 (8.79–30.73)	9.26 (2.85–22.50)

Table 2

The positive rates of serology between the symptomatic group and asymptomatic group

	Symptomatic group		Asymptomatic froup		χ 2	p value
	n = 54 (%)	Clopper–Pearson 95% CI	n = 13 (%)	Clopper–Pearson 95% CI
IgG+	43 (79.6%)	66.5%–89.4%	10 (76.9%)	46.2%–95.0%	0.000	1.000
IgM+	13 (24.1%)	13.5%–37.6%	2 (15.4%)	1.9%–45.4%	0.093	0.761
Neutralization antibodies+	40 (74.1%)	60.3%– 85.0%	5 (38.5%)	13.9%–68.4%	4.519	0.034*

Abbreviation: CI, confidence interval.

p < 0.05.

In our study, most participants infected with SARS‐CoV‐2 maintained a relatively higher level of IgG and neutralizing antibodies 1 year after primary infection than that of IgM. The most abundant antibody type is IgG, which can provide lasting immunity, and IgM titers decay rapidly. The neutralizing antibodies reflect the protective immune responses against SARS‐CoV‐2. Lau et al. found that neutralizing antibody titers lasted beyond 6 months in most COVID‐19 patients, and Han et al. reported similar results in severe COVID‐19 patients. According to the recent study by He et al., the neutralizing antibody could last at least 9 months following diagnosis among 41.2% of COVID‐19 patients, which was relatively lower than the results of our study (67.2%). The potential reason for the slight differences may be the much higher proportion of asymptomatic infections than our study. In general, the possibility of reinfection of SARS‐CoV‐2 would be greatly reduced 1 year after onset. Elucidating the long‐term changes of antibodies can reveal the prognosis of COVID‐19 and evaluate the patients' immunity against SARS‐CoV‐2, but also contribute to the practical application of vaccines. Sixty‐seven percent of individuals have neutralizing antibodies after 1 year, which may mean that all need to be vaccinated to bring that percentage further up.

We found that the symptomatic patients had significantly higher positive of neutralizing antibody compared to asymptomatic patients, while no statistical significance for IgG and IgM. Several studies found that the high neutralizing antibody titer is related to severe disease. , The neutralizing antibody in asymptomatic patients may be more likely to decrease over time than that in symptomatic patients because the initial immune response was much slighter in asymptomatic patients.

Limitations of our study are the relatively small sample size and the lack of samples from earlier time points available for comparative antibody measurements. And there were no validation data sheets available for the assay. In this study, only those who were detected SARS‐CoV‐2 were included and lacked a healthy control group. The limitations of serological testing need to be recognized because the laboratory methods vary.

In conclusion, our results identified that SARS‐CoV‐2 infection elicits IgG and neutralizing antibodies in most individuals that last beyond one year. The findings provide great insight for a better understanding of the humoral immunity against SARS‐CoV‐2 and would contribute to the practical application of vaccines.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

AUTHOR CONTRIBUTIONS

Conception or design of the work: Changzheng Chen, Lijuan Xu, and Lu He. Data collection and data analysis: Cheng Zeng, Wanzhou Xu, Ying Li, Xiaojie Xie, Wei Xu, Hongmiao Xia, Fengjuan Tang and Shiqi Tang. Drafting the article: Lu He and Cheng Zeng. Review and editing: Lu He and Yuyang Zeng. All authors approved the final version of the manuscript for publication.