Department of Medical Microbiology & Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
PLoS One. 2024 Jul 15;19(7):e0304990. doi: 10.1371/journal.pone.0304990. eCollection 2024.
After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC.
RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects.
186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks.
Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC.
COVID-19 初始感染后，免疫失调可能持续存在，并导致 COVID-19 的急性后期后遗症（PASC）。我们描述了成年人在 SARS-CoV-2 感染后长达 6 个月的细胞因子纵向轨迹，并探索了 PASC 的早期预测因子。
RECOVERED 是一项前瞻性队列研究，纳入了 2020 年 5 月至 2021 年 6 月在荷兰阿姆斯特丹实验室确诊的 SARS-CoV-2 感染患者。在随访的第 4、12 和 24 周采集血清。自 COVID-19 发病后第 2 个月起每月完成症状问卷；在 6 个月时测试肺扩散能力（DLCO）。通过人类磁性 Luminex 筛选测定法分析细胞因子浓度。我们使用线性混合效应模型来研究细胞因子的对数浓度随时间的变化，并评估它们与社会人口统计学和临床特征的关联，这些特征作为固定效应纳入模型。
186/349（53%）名参与者有≥2 份血清样本，纳入当前分析。其中，101/186（54%：45/101[45%]为女性，中位年龄 55 岁[IQR=45-64]）在 COVID-19 发病后 12 和 24 周报告有 PASC。我们纳入了 37 份参考样本（17/37[46%]为女性，中位年龄 49 岁[IQR=40-56]）。在多变量模型中，PASC 与 CRP 升高和扩散能力异常相关，在 24 周时与升高的 IL10、IL17、IL6、IP10 和 TNFα相关。COVID-19 发病时早期（0-4 周）的 IL-1β和 BMI 是预测 24 周 PASC 的指标。
我们的研究结果表明，免疫失调在 PASC 的发病机制中起着重要作用，特别是在肺功能下降的个体中。早期的 IL-1β有望成为 PASC 的预测指标。
