{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:27:20Z","timestamp":1784543240344,"version":"3.55.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["81525023"],"award-info":[{"award-number":["81525023"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children\u2019s health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Random-intercept modeling with B-spline was conducted to characterize NAb response kinetics. The NAb titer of CVA16 infection patients was estimated to increase from negative (2.1, 95% confidence interval [CI]: 1.4\u20133.3) on the day of onset to a peak of 304.8 (95% CI: 233.4\u2013398.3) on day 21 and then remained &amp;gt;64 until 26 mo after onset. However, the NAb response level of EV-A71\u2013infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71\u2013infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4\u20133.2) increase. When a 4-fold rise in titer was used as the criterion for serological diagnosis of CVA16 and EV-A71 infection, acute-phase serum needs to be collected at 0\u20135 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6\u201327.4) and 24.4 d (95% CI: 15.3\u201338.3) after onset, respectively. In conclusion, both CVA16 and EV-A71 infection induce a persistent humoral immune response but have different NAb response levels and paired-serum sampling times for serological diagnosis. Clinical severity can affect the anti\u2013EV-A71 NAb response.<\/jats:p>","DOI":"10.4049\/jimmunol.2200143","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T15:15:12Z","timestamp":1657811712000},"page":"280-287","source":"Crossref","is-referenced-by-count":7,"title":["Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017\u20132019"],"prefix":"10.1093","volume":"209","author":[{"given":"Yonghong","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Yang","sequence":"additional","affiliation":[{"name":"Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital , Zhengzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital , Zhengzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liang","sequence":"additional","affiliation":[{"name":"West China School of Public Health, Sichuan University , Sichuan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital , Zhengzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongchen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital , Zhengzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1673-6819","authenticated-orcid":false,"given":"Justin Jang Hann","family":"Chu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology and Infectious Disease Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore , Singapore,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-5648","authenticated-orcid":false,"given":"Hongjie","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2025021008204895800_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S2352-4642(19)30065-3","article-title":"Remaining challenges for prevention and control of hand, foot, and mouth disease","volume":"3","author":"Yu","year":"2019","journal-title":"Lancet Child Adolesc. 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