To the Editor: Previous studies have demonstrated that IgG andneutralizing antibodies against coronavirus associated withthe severe acute respiratory syndrome (SARS) may persist, inspite of a decline in titer, for 2 years in patients who haverecovered from SARS.1,2 For 3 years, we followed patients whohad recovered from infection with SARS-associated coronavirus,to measure the longevity of specific antibodies.
Fifty-six patients who were positive for serum IgG and neutralizingantibodies against SARS-associated coronavirus at the time ofrecovery from acute SARS infection were included in this study.1The titers of IgG and neutralizing antibodies were significantlycorrelated during the 3-year follow-up period (Spearman's correlationcoefficient, 0.905; P=0.002). The titers peaked at month 4 anddiminished thereafter (Figure 1). IgG and neutralizing antibodieswere undetectable in 19.4% and 11.1% of serum samples, respectively,at month 30, and in 25.8% and 16.1%, respectively, at month36. For the IgG antibody, the geometric mean reciprocal titersdropped from 244 at month 4 to 34 at month 30 and 28 at month36. For the neutralizing antibody, the geometric mean reciprocaltiters dropped from 1232 at month 4 to 32 at month 30 and remainedat that value through month 36. There were no significant differencesin the kinetics of specific antibodies according to diseaseseverity, duration of hospitalization, type and number of coexistingconditions, or use or nonuse of corticosteroids. However, the19 patients with subsequent aseptic femoral neck necrosis hadsignificantly lower neutralizing antibody levels than the 37without the sequela (P<0.001, from mixed-linear random-effectsmodels).
Figure 1. Temporal Changes in IgG and Neutralizing Antibodies against SARS-Associated Coronavirus among Patients Who Recovered from SARS.
The IgG and neutralizing antibodies against SARS-associated coronavirus were detected with an enzyme-linked immunosorbent assay and a conventional neutralization assay, respectively, of SARS-associated coronavirus BJ01 strain (GenBank accession number AY278488
[GenBank]
) from tissue cultures.1 The percentages of serum samples that were positive for the antibody (blue line) and the geometric mean reciprocal titers (red line) are shown for the IgG antibody (Panel A) and for the neutralizing antibody (Panel B). The IgG and neutralizing antibodies were considered positive when their titers were greater than 1:10. I bars indicate standard deviations.
Experiments in animals indicate that IgG and neutralizing antibodies,along with T-cell mediated immunity, are essential for protectionagainst live-virus challenge.3,4 Our data suggest that immuneprotection may wane over time, as demonstrated in patients infectedwith human coronavirus 229E.5 How this waning humoral immunitymay affect future SARS-associated disease in the context ofreexposure to SARS is unknown. In the absence of another SARSoutbreak, we do not know whether lower or even undetectablelevels of specific antibodies would be adequate to protect aperson from reinfection due to a potential anamnestic response,as seen with other viral infections such as measles and hepatitisA. The implications of the lower neutralizing antibody levelsin 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{at}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 Communityand the National 863 High-Tech Program of China.
No potential conflict of interest relevant to this letter wasreported.
References
Liu W, Fontanet A, Zhang PH, et al. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis 2006;193:792-795. [CrossRef][Web of Science][Medline]
Mo H, Zeng G, Ren X, et al. Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Respirology 2006;11:49-53. [CrossRef][Web of Science][Medline]
Yang ZY, Kong WP, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004;428:561-564. [CrossRef][Medline]
Subbarao K, McAuliffe J, Vogel L, et al. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J Virol 2004;78:3572-3577. [Free Full Text]
Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect 1990;105:435-446. [Medline]
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