Delayed Mucosal Antiviral Responses Despite Robust Peripheral Inflammation in Fatal COVID-19
Delayed Mucosal Antiviral Responses Despite Robust Peripheral Inflammation in Fatal COVID-19
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尽管致命的 COVID-19 患者存在严重的外周炎症，但粘膜抗病毒反应仍延迟
DOI：
10.1093/infdis/jiad590
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Sidhu J
中科院分区：
文献类型：
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作者：
Sidhu J
背景严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在外周血液中的炎症和免疫反应已被广泛描述，但在最初感染的上呼吸道粘膜部位的反应相对较少。我们试图确定区分2019年冠状病毒病(新冠肺炎)严重程度的黏膜细胞因子/趋化因子特征，并将其与疾病进展和外周炎症联系起来。分析考虑了疾病期间的采样时间，分为早期(症状出现后0-5天)和晚期(症状出现后6-20天)。结果在严重新冠肺炎存活的患者在感染早期显示干扰素主导的黏膜免疫反应(干扰素-γ、CXCL10和CXCL13)。尽管SARS-CoV-2病毒载量相当，但这些早期粘膜反应在那些将进展为致命疾病的患者中缺失。白介素2(IL-2)、白介素10(IL-10)、干扰素-γ和白介素12p70(IL-12p70)在晚期疾病的粘膜炎症中占主导地位，它们随病情严重程度而变化，但并不能区分患者的生存或死亡。黏膜中的细胞因子和趋化因子与外周血中明显的细胞因子和趋化因子反应不同，特别是在致死性疾病期间。结论早期黏膜抗病毒反应缺陷可预测致死性新冠肺炎，但与病毒载量无关。早期粘膜免疫反应可能决定了重症新冠肺炎的发病轨迹。
BackgroundWhile inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.MethodsWe 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.ResultsPatients 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.ConclusionsDefective 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.