{'fraction_non_alphanumeric': 0.05129390018484288, 'fraction_numerical': 0.05730129390018484, 'mean_word_length': 4.835579514824798, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
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, 2017–2019

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’s 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]: 1.4–3.3) on the day of onset to a peak of 304.8 (95% CI: 233.4–398.3) on day 21 and then remained >64 until 26 mo after onset. However, the NAb response level of EV-A71–infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71–infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4–3.2) 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 0–5 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6–27.4) and 24.4 d (95% CI: 15.3–38.3) 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–EV-A71 NAb response. Key Points Both CVA16 and EV-A71 infection induced a persistent humoral immune response. Compared with EV-A71 infection, the CVA16-induced NAb response was significantly lower. Our findings showed that sampling time and clinical severity had effects on the NAb response.