METHODS: We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days after symptom onset) or late (6-20 days after symptom onset) phase.
RESULTS: Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease.
CONCLUSIONS: Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.
方法:我们检测了274例COVID-19住院患者鼻腔样本中的35种细胞因子和趋化因子。分析考虑了疾病期间的采样时间,如早期(症状发作后0-5天)或晚期(症状发作后6-20天)阶段。
结果:重度COVID-19存活的患者表现出干扰素(IFN)主导的粘膜免疫反应(IFN-γ,CXCL10和CXCL13)在感染早期。尽管SARS-CoV-2病毒载量相等,但仍将发展为致命疾病的患者中没有这些早期粘膜反应。晚期疾病的黏膜炎症以白细胞介素2(IL-2)为主,IL-10,IFN-γ,和IL-12p70,其与严重程度成比例,但不能区分存活或死于疾病的患者。粘膜中的细胞因子和趋化因子与外周血中明显的反应有区别,特别是在致命疾病期间。
结论:早期粘膜抗病毒反应缺陷会导致致命的COVID-19,但与病毒载量无关。早期粘膜免疫反应可能定义严重COVID-19的轨迹。