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Neutralizing antibody response and SARS severity.

Ho MS, Chen WJ, Chen HY, Lin SF, Wang MC, Di J, Lu YT, Liu CL, Chang SC, Chao CL, King CC, Chiou JM, Su IJ, Yang JY - Emerging Infect. Dis. (2005)

Bottom Line: Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes.Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008).Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

View Article: PubMed Central - PubMed

Affiliation: Academia Sinica, Taipei, Taiwan.

ABSTRACT
Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

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Related in: MedlinePlus

Scatterplot of antibody titers of the 247 seropositive study participants (titers of the same participant measured at different times are connected); superimposed is the fitted mean curve (in red) of log2 (antibody titer) between weeks 3 and 13 postinfection based on the linear mixed model by severity (duration of illness) and sex at the median age of 36 years. Each dot represents >1 titer; no distinction is made between single values and those with >1 value.
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Figure 3: Scatterplot of antibody titers of the 247 seropositive study participants (titers of the same participant measured at different times are connected); superimposed is the fitted mean curve (in red) of log2 (antibody titer) between weeks 3 and 13 postinfection based on the linear mixed model by severity (duration of illness) and sex at the median age of 36 years. Each dot represents >1 titer; no distinction is made between single values and those with >1 value.

Mentions: Because of the differences in the distribution of age and sex among patient groups and the differences in the number and timing of specimens collected for antibody measurement, we used regression-based modeling approach to examine these factors simultaneously and tried to analyze the relationship between their potential interactions and antibody titers (Table 5, Figure 2A). This model was based on the neutralizing antibody titer of the 312 convalescent-phase serum assays, representing 194 patients who had had 1 convalescent-phase serum sample collected between weeks 3 to 12 after onset of fever, 41 patients who had 2 convalescent-phase samples, and 12 patients who had 3. The number of serum specimens collected ranged from 21 to 43 per week from week 4 of illness through week 12. The model suggested that neutralizing antibody rose and diminished during the follow-up period between weeks 3 and 13 after onset of illness (p = 0.026 for linear term and p = 0.042 for quadratic term); the estimated half life was ≈6.4 weeks. Patients with a more protracted clinical course tended to have a higher antibody titer than patients with a shorter clinical course (p = 0.008). Antibody in patients with more severe clinical courses tended to decay at a faster rate than in patients with shorter clinical course (the interaction between duration of illness and time of serum collection, p = 0.037). This pattern of decay followed a half-life of ≈6.4 weeks after reaching the peak, which occurred between weeks 5 and 8 after infection (Figure 2B). The time that the blood was collected for each patient was examined, and an equally dispersed pattern of blood collection was found in all clinical groups (Figure 3).


Neutralizing antibody response and SARS severity.

Ho MS, Chen WJ, Chen HY, Lin SF, Wang MC, Di J, Lu YT, Liu CL, Chang SC, Chao CL, King CC, Chiou JM, Su IJ, Yang JY - Emerging Infect. Dis. (2005)

Scatterplot of antibody titers of the 247 seropositive study participants (titers of the same participant measured at different times are connected); superimposed is the fitted mean curve (in red) of log2 (antibody titer) between weeks 3 and 13 postinfection based on the linear mixed model by severity (duration of illness) and sex at the median age of 36 years. Each dot represents >1 titer; no distinction is made between single values and those with >1 value.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367364&req=5

Figure 3: Scatterplot of antibody titers of the 247 seropositive study participants (titers of the same participant measured at different times are connected); superimposed is the fitted mean curve (in red) of log2 (antibody titer) between weeks 3 and 13 postinfection based on the linear mixed model by severity (duration of illness) and sex at the median age of 36 years. Each dot represents >1 titer; no distinction is made between single values and those with >1 value.
Mentions: Because of the differences in the distribution of age and sex among patient groups and the differences in the number and timing of specimens collected for antibody measurement, we used regression-based modeling approach to examine these factors simultaneously and tried to analyze the relationship between their potential interactions and antibody titers (Table 5, Figure 2A). This model was based on the neutralizing antibody titer of the 312 convalescent-phase serum assays, representing 194 patients who had had 1 convalescent-phase serum sample collected between weeks 3 to 12 after onset of fever, 41 patients who had 2 convalescent-phase samples, and 12 patients who had 3. The number of serum specimens collected ranged from 21 to 43 per week from week 4 of illness through week 12. The model suggested that neutralizing antibody rose and diminished during the follow-up period between weeks 3 and 13 after onset of illness (p = 0.026 for linear term and p = 0.042 for quadratic term); the estimated half life was ≈6.4 weeks. Patients with a more protracted clinical course tended to have a higher antibody titer than patients with a shorter clinical course (p = 0.008). Antibody in patients with more severe clinical courses tended to decay at a faster rate than in patients with shorter clinical course (the interaction between duration of illness and time of serum collection, p = 0.037). This pattern of decay followed a half-life of ≈6.4 weeks after reaching the peak, which occurred between weeks 5 and 8 after infection (Figure 2B). The time that the blood was collected for each patient was examined, and an equally dispersed pattern of blood collection was found in all clinical groups (Figure 3).

Bottom Line: Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes.Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008).Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

View Article: PubMed Central - PubMed

Affiliation: Academia Sinica, Taipei, Taiwan.

ABSTRACT
Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

Show MeSH
Related in: MedlinePlus