Herrero Rolando, Fantin Romain, Loría Viviana, Aparicio Amada, Prevots D Rebecca, Zúñiga Michael, Wong Roy, Morera Melvin, Butt Julia, Binder Marco, Abdelnour Arturo, Calderón Alejandro, Castro Roberto, Cortes Bernal, Ocampo Rebeca, Vanegas Juan Carlos, Gail Mitchell H, Pfeiffer Ruth M, Flock Julia, Remans Kim, Eberhardt Lukas, Rastgou Soheil, Magalhaes Vladimir, Porras Carolina, Hildesheim Allan, Waterboer Tim
Agencia Costarricense de Investigaciones Biomédicas-Fundación INCIENSA (ACIB-FUNIN), San José, Costa Rica.
Caja Costarricense del Seguro Social, San José, Costa Rica.
BMC Infect Dis. 2025 Mar 18;25(1):376. doi: 10.1186/s12879-025-10742-8.
Antibodies to SARS-CoV-2 are essential for protection or reduction in severity of subsequent disease. We studied antibody responses to spike protein receptor-binding domain (S1-RBD) and nucleocapsid (N) in a population-based sample of COVID-19 cases in Costa Rica.
As part of the RESPIRA study, we selected an age-stratified random sample of PCR-confirmed COVID-19 cases diagnosed from March 2020 to July 2021. Antibodies were determined with multiplex serology in 794 unvaccinated subjects diagnosed 3 days to 17 months before recruitment to investigate immune response to natural infection. In addition, neutralizing antibodies were determined in 136 randomly selected participants. We estimated antibody positivity and GMTs by time since diagnosis and explored determinants using multivariate regression.
Most participants tested 15-29 days after PCR diagnosis were seropositive for N (90%) and S1-RBD antibodies (96%) and had the highest GMTs for both antibodies. Only 42% of subjects tested one year after infection were seropositive for N antibodies, compared to 97% for S1-RBD. GMTs for neutralizing antibodies peaked 15-89 days after infection and declined but remained positive for 95% of subjects thereafter. In multivariate models, antibodies were significantly higher among men and increased with age and severity of the clinical presentation. The correlation of multiplex and neutralizing antibodies was high (0.72 [95% CI = 0.63-0.79]) and stronger among women.
A robust immune response against N and S1-RBD is elicited by COVID-19 a few days after infection. While S1-RBD antibodies are present after > 1 year, N antibodies decline significantly. Antibody levels are higher in men and increase with age and severity of disease. The different immune response patterns by sex warrant further investigation.
RESPIRA Study ClinicalTrials.gov ID: NCT04537338 (3 September 2020).
针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的抗体对于预防或减轻后续疾病的严重程度至关重要。我们在哥斯达黎加的一组基于人群的新冠肺炎病例样本中研究了针对刺突蛋白受体结合域（S1-RBD）和核衣壳（N）的抗体反应。
作为RESPIRA研究的一部分，我们选取了2020年3月至2021年7月期间经聚合酶链反应（PCR）确诊的新冠肺炎病例的年龄分层随机样本。在794名未接种疫苗的受试者中采用多重血清学方法检测抗体，这些受试者在入组前3天至17个月被诊断为新冠肺炎，以研究对自然感染的免疫反应。此外，在136名随机选择的参与者中检测了中和抗体。我们根据诊断后的时间估计抗体阳性率和几何平均滴度（GMT），并使用多变量回归探索其决定因素。
大多数在PCR诊断后15至29天进行检测的参与者，其N抗体（90%）和S1-RBD抗体（96%）呈血清阳性，且两种抗体的GMT最高。感染后一年进行检测的受试者中，只有42%的N抗体呈血清阳性，而S1-RBD抗体的这一比例为97%。中和抗体的GMT在感染后15至89天达到峰值，随后下降，但此后95%的受试者仍呈阳性。在多变量模型中，男性的抗体水平显著更高，且随年龄和临床表现的严重程度增加。多重抗体和中和抗体之间的相关性很高（0.72 [95%置信区间=0.63-0.79]），在女性中更强。
新冠肺炎感染后数天会引发针对N和S1-RBD的强大免疫反应。虽然感染一年后仍存在S1-RBD抗体，但N抗体显著下降。男性的抗体水平更高，且随年龄和疾病严重程度增加。不同性别间的免疫反应模式值得进一步研究。
RESPIRA研究，ClinicalTrials.gov标识符：NCT04537338（2020年9月3日）。
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