Neutralizing antibody response and SARS severity

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.

Figure 1

Positive rate of severe acute respiratory syndrome–associated coronavirus titer by sex and age.

Figure 2

A) Perspective surfaces of neutralizing antibody titer (dilution) based on the fitted linear mixed model in Table 5. The median age was 36 years for men (left panel) and for women (right panel). B) Cross-sectional curves of neutralizing antibody titer (dilution) extracted from panel A with duration of illness set at 10, 17, 24, and 31 days, respectively, for men (left panel) and women (right panel); the vertical lines mark peak titer times.

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.