Correspondence

Disappearance of Antibodies to SARS-Associated Coronavirus after Recovery

N Engl J Med 2007; 357:1162-1163September 13, 2007

Article

To the Editor:

Previous studies have demonstrated that IgG and neutralizing antibodies against coronavirus associated with the severe acute respiratory syndrome (SARS) may persist, in spite of a decline in titer, for 2 years in patients who have recovered from SARS.1,2 For 3 years, we followed patients who had recovered from infection with SARS-associated coronavirus, to measure the longevity of specific antibodies.

Fifty-six patients who were positive for serum IgG and neutralizing antibodies against SARS-associated coronavirus at the time of recovery from acute SARS infection were included in this study.1 The titers of IgG and neutralizing antibodies were significantly correlated during the 3-year follow-up period (Spearman's correlation coefficient, 0.905; P=0.002). The titers peaked at month 4 and diminished thereafter (Figure 1Figure 1Temporal Changes in IgG and Neutralizing Antibodies against SARS-Associated Coronavirus among Patients Who Recovered from SARS.). IgG and neutralizing antibodies were undetectable in 19.4% and 11.1% of serum samples, respectively, at month 30, and in 25.8% and 16.1%, respectively, at month 36. For the IgG antibody, the geometric mean reciprocal titers dropped from 244 at month 4 to 34 at month 30 and 28 at month 36. For the neutralizing antibody, the geometric mean reciprocal titers dropped from 1232 at month 4 to 32 at month 30 and remained at that value through month 36. There were no significant differences in the kinetics of specific antibodies according to disease severity, duration of hospitalization, type and number of coexisting conditions, or use or nonuse of corticosteroids. However, the 19 patients with subsequent aseptic femoral neck necrosis had significantly lower neutralizing antibody levels than the 37 without the sequela (P<0.001, from mixed-linear random-effects models).

Experiments in animals indicate that IgG and neutralizing antibodies, along with T-cell mediated immunity, are essential for protection against live-virus challenge.3,4 Our data suggest that immune protection may wane over time, as demonstrated in patients infected with human coronavirus 229E.5 How this waning humoral immunity may affect future SARS-associated disease in the context of reexposure to SARS is unknown. In the absence of another SARS outbreak, we do not know whether lower or even undetectable levels of specific antibodies would be adequate to protect a person from reinfection due to a potential anamnestic response, as seen with other viral infections such as measles and hepatitis A. The implications of the lower neutralizing antibody levels in patients with aseptic femoral neck necrosis are unclear.

Wu-Chun Cao, M.D., Ph.D.
Wei Liu, M.D., Ph.D.
State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China
caowc@nic.bmi.ac.cn

Pan-He Zhang, M.Sc.
Fang Zhang, M.D.
Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China

Jan H. Richardus, M.D., Ph.D.
Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands

Supported by grants from the Commission of the European Community and the National 863 High-Tech Program of China.

No potential conflict of interest relevant to this letter was reported.

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Citing Articles (4)

Citing Articles

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   Kai Zhao, Hui Wang, Changyou Wu. (2011) The immune responses of HLA-A*0201 restricted SARS-CoV S peptide-specific CD8+ T cells are augmented in varying degrees by CpG ODN, PolyI:C and R848. Vaccine 29:38, 6670-6678
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   Lifeng Liu, Jing Xie, Jianpin Sun, Yang Han, Chao Zhang, Hongwei Fan, Zhengyin Liu, Zhifeng Qiu, Yuxian He, Taisheng Li. (2011) Longitudinal profiles of immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus components and neutralizing activities in recovered patients. Scandinavian Journal of Infectious Diseases 43:6-7, 515-521
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   Yan-Ying Fan, Zi-Tong Huang, Li Li, Man-Hui Wu, Tao Yu, Richard A. Koup, Robert T. Bailer, Chang-You Wu. (2009) Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection. Archives of Virology 154:7, 1093-1099
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4. 4

   Nan-Shan ZHONG, Guang-Qiao ZENG. (2008) Pandemic planning in China: Applying lessons from severe acute respiratory syndrome. Respirology 13:s1, S33-S35
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