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Are clinical characteristics of patients who recovered from mild coronavirus disease 2019 (COVID-19) associated with levels of neutralizing antibodies?
In this cohort study of 175 patients who recovered from mild COVID-19, neutralizing antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varied substantially at the time of discharge. In addition, neutralizing antibodies were not detected in 10 patients.
Further research is needed to understand the implications of variable levels of SARS-CoV-2–specific neutralizing antibodies for protection against future infections with SARS-CoV-2.
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.
To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19.
Design, Setting, and Participants
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.
SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase–polymerase chain reaction testing of nasopharyngeal samples.
Main Outcomes and Measures
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.
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, <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 (r = 0.451; 95% CI, 0.320-0.564; P < .001), receptor binding domain (r = 0.484; 95% CI, 0.358-0.592; P < .001), and S2 regions (r = 0.346; 95% CI, 0.204-0.473; P < .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; P = .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; P = .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; P < .001; middle-aged vs younger: median difference, 832; 95% CI, 284-1013; P < .001). The NAb titers were correlated with plasma C-reactive protein levels (r = 0.508; 95% CI, 0.386-0.614; P < .001) and negatively correlated with lymphocyte counts (r = −0.427; 95% CI, −0.544 to −0.293; P < .001) at the time of admission.
Conclusions and Relevance
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.
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Accepted for Publication: July 19, 2020.
Published Online: August 18, 2020. doi:10.1001/jamainternmed.2020.4616
Correction: This article was corrected on October 5, 2020, to fix an error in the Results section of the Abstract.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Wu F et al. JAMA Internal Medicine.
Corresponding Author: Jinghe Huang, PhD, Shanghai Public Health Clinical Center and Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, China (firstname.lastname@example.org); Fan Wu, PhD (email@example.com).
Author Contributions: Drs Huang and Fan Wu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: F. Wu, Gu, Zhu, H. Lu, Wen, Huang.
Acquisition, analysis, or interpretation of data: F. Wu, Liu, A. Wang, L. Lu, Q. Wang, Chen, Y. Wu, Xia, Ling, Y. Zhang, Xun, R. Zhang, Xie, Jiang, Huang.
Drafting of the manuscript: F. Wu, L. Lu, Gu, Y. Wu, Ling, Huang.
Critical revision of the manuscript for important intellectual content: F. Wu, Liu, A. Wang, Q. Wang, Chen, Xia, Y. Zhang, Xun, R. Zhang, Xie, Jiang, Zhu, H. Lu, Wen, Huang.
Statistical analysis: F. Wu, Liu, Gu, Ling, Y. Zhang, Huang.
Obtained funding: F. Wu, Huang.
Administrative, technical, or material support: F. Wu, Liu, A. Wang, L. Lu, Q. Wang, Chen, Xia, Y. Zhang, Xun, R. Zhang, Xie, Jiang, Huang.
Supervision: F. Wu, Zhu, H. Lu, Wen, Huang.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by the National Major Science and Technology Projects of China (grants 2017ZX10202102 and 2018ZX10301403), National Natural Science Foundation of China (grant 31771008), Hundred Talent Program of Shanghai Municipal Health Commission (grant 2018BR08), and the Chinese Academy of Medical Sciences (grant 2019PT350002).
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Vanessa M. Hirsch, PhD, DVM (National Institute of Allergy and Infectious Diseases, National Institutes of Health), reviewed the manuscript. Neither Dr Hirsch nor the National Institutes of Health received any compensation for her review.
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