Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China
Authors: Fan Wu, Mei Liu, Aojie Wang, Lu Lu, Qimin Wang, Chenjian Gu, Jun Chen, Yang Wu, Shuai Xia, Yun Ling, Yuling Zhang, Jingna Xun, Rong Zhang, Youhua Xie, Shibo Jiang, Tongyu Zhu, Hongzhou Lu, Yumei Wen, Jinghe Huang
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. <h3>Objective</h3> To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19. <h3>Design, Setting, and Participants</h3> In this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China. <h3>Exposures</h3> SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase–polymerase chain reaction testing of nasopharyngeal samples. <h3>Main Outcomes and Measures</h3> The primary outcome was SARS-CoV-2–specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level. <h3>Results</h3> Of the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2–specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, &lt;40), and 2 patients who showed very high titers of NAbs, with ID50 levels of 15 989 and 21 567. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. NAbs were unable to cross-react with SARS-associated CoV and NAb titers correlated with the spike-binding antibodies targeting S1 (<i>r</i> = 0.451; 95% CI, 0.320-0.564;<i>P</i> &lt; .001), receptor binding domain (<i>r</i> = 0.484; 95% CI, 0.358-0.592;<i>P</i> &lt; .001), and S2 regions (<i>r</i> = 0.346; 95% CI, 0.204-0.473;<i>P</i> &lt; .001). NAb titers at the time of discharge were significantly higher in the 82 men (1417 [IQR, 541-2253]) than those in the 93 women (905 [IQR, 371-1687]) (median difference, 512; 95% CI, 82-688;<i>P</i> = .01) and at the time of follow-up in 56 male patients (1049 [IQR, 552-2454]) vs 61 female patients (751 [IQR, 216-1301]) (median difference, 298; 95% CI, 86-732;<i>P</i> = .009). Plasma NAb titers were significantly higher in 56 older (1537 [IQR, 877-2427) and 63 middle-aged (1291 [IQR, 504-2126]) patients than in 56 younger patients (459 [IQR, 225-998]) (older vs younger: median difference, 1078; 95% CI, 548-1287;<i>P</i> &lt; .001; middle-aged vs younger: median difference, 832; 95% CI, 284-1013;<i>P</i> &lt; .001). The NAb titers were correlated with plasma C-reactive protein levels (<i>r</i> = 0.508; 95% CI, 0.386-0.614;<i>P</i> &lt; .001) and negatively correlated with lymphocyte counts (<i>r</i> = −0.427; 95% CI, −0.544 to −0.293;<i>P</i> &lt; .001) at the time of admission. <h3>Conclusions and Relevance</h3> In this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.